Index

A ATR. See ATM-and Rad3-related (ATR) Acetylation , 99–100 ATRX remodeler , 469 Actin and actin-related proteins in Remodeler ATRX-syndrome and α-thalassemia regulation , 97–98 myelodysplasia (ATMDS) Adaptors to machineries , 368 syndrome , 124–125 ADP-ribosyltransferase Diphtheria toxin-like Automodifi cation domain (AMD) , 312 (ARTD) , 316–318 AMD. See Automodifi cation domain (AMD) Arabidopsis thaliana B E3 ubiquitin-protein isopeptide ligases , 271 BAH domain. See Bromo-Adjacent Homology histone and DNA methylation connection , (BAH) domain 241–242 Base excision repair (BER) pathway , 326 RNF2 and PRC1 complex subunits , 271 53BP1, potential PTM reader , 361 Architectural proteins , 367 Brahma homologue (BRM) , 500 Arginine methylation , 246–247 BRCA1 C terminus (BRCT) , 312 ARTD. See ADP-ribosyltransferase Diphtheria BRCA1, heterochromatic ubiquitylation of toxin-like (ARTD) H2A , 270 Ataxia telangiectasia-mutated (ATM) , BRCT. See BRCA1 C terminus (BRCT) 496, 511, 513 BRM. See Brahma homologue (BRM) ATM-and Rad3-related (ATR) , 496, 511, 513 Bromo-Adjacent Homology (BAH) domain, 498 ATM/ATR signaling Bromodomains E3 ligases RNF2 , 296 acetylated histone substrates binding , mammalian cells , 295–296 84, 165 RING fi nger domain , 296 acetylation mark , 151–152 RNF8 , 296 BRD fold , 164 UV irradiation , 295 cellular process , 165 ATP-dependent chromatin remodeling human, classifi cation , 164 complexes SWI/SNF-family Remodelers , 85 DNA replication , 515 Bur1/Bur2 (BUR) cyclindependent protein fork progression , 519 kinase complex , 278–280 initiation and completion , 521 INO80 , 503, 516 S. cerevisiae , 502 C SNF2h study , 518 Carboxy-terminal domain (CTD) , 280 SWI/SNF family , 493 CARM1. See Coactivator-associated arginine transcriptional regulation and chromosome methyltransferase 1 (CARM1) transmission, 501 CCCTC-binding factor (CTCF) , 326–327

J.L. Workman and S.M. Abmayr (eds.), Fundamentals of Chromatin, 573 DOI 10.1007/978-1-4614-8624-4, © Springer Science+Business Media New York 2014 574 Index

Cellular metabolism nucleosomes , 330–332 5' adenosine monophosphate (AMP) , 563 open chromatin and gene expression , amino acid metabolism , 563–564 319–320 glycolysis , 561 PARylation , 330 H2BS36 phosphorylation , 563 posttranslational modifi cations , 332–333 H3K4me2 and H3K4me3 , 564 regulatory inputs and outputs , 335 nucleosomes , 561 remodelers , 324–325 PKM2 , 564 SAPKs , 555–557 threonine metabolisms and chromatin signals , 555 regulations , 561–563 stress signaling, S-phase progression and CenH3 chaperones TAR , 557–558 mammalian HJURP , 44–45 Chromatin access mechanisms and regulation , Scm3 , 45–46 89, 92 CenH3-H4 deposition Chromatin architecture CENP-A incorporation , 393–394 ChIP-chip and ChIP-Seq , 440 CENP-A protein , 393 nucleosomal patterning , 440 centromeric DNA replication , 394–395 nucleosome depleted regions , 441 chaperones , 394 RNAPII-mediated transcription , 440 fl uorescence recovery after photobleaching yeast genes, nucleosomal organization , 441 (FRAP) , 393 Chromatin assembly and disassembly during GTPase activating protein (GAP) , 394 DNA repair Holliday Junction-Recognizing Protein “Access, Repair, Restore” model , 54 (HJURP), 394 BER and NER , 53–54 Centromeric chromatin reassembly CAF-1 , 55 CenH3 chaperones , 44–46 H2A.X role , 54–55 centromere-specifi c histone H3 variant , 43 H2A.Z incorporation , 54 DNA composition , 44 H3K56ac , 55 fl uorescent pulse-labeling experiments, pathways , 53 HeLa cells, 44 Chromatin editing involving H2A variants , 94–95 Cerebro-oculo-facio-skeletal (COFS) Chromatin immunoprecipitation (ChIP) syndrome , 125 assays, 495, 498 CHARGE syndrome , 125–126 Chromatin modifi ers (histone PTM cross-talk) CHD domain , 85–86 antagonism , 369–370 CHD family , 81–82 counter antagonism , 369, 371 CHD remodelers , 111 epistasis relationship , 368–369 ChIP assays. See Chromatin parallel reinforcement , 369–370 immunoprecipitation (ChIP) assays positive feedback , 369–370 Chromatin Chromatin processes and Remodeler functions access , 75 access , 75 assembly mechanisms and regulation , 92–94 deposition and assembly , 73–74 cellular metabolism , 561–564 editing , 74 circadian rhythm Chromatin remodelers circadian transcription factors , 565–567 histone deacetylation , 454 period and cryptochrome , 565 H3 K36 methylation , 463–464 RNA polymerase II , 565–567 Hrp1 , 454–455 deposition and assembly , 73–74 nucleosomal organization , 455 DNA methylation , 565, 567 NuRD , 454 editing , 74 recruitment , 458 epigenetics and aging , 568–569 remodeling activity, regulation ncRNAs (see Noncoding RNAs (ncRNAs)) histone PTMs , 458–459 PARP-1 functions remodeler PTMs , 459 cellular signaling pathways , 333–334 SNF2 family , 454 nonhistone protein-binding partners , as transcription regulators 332–333 Chd and Iswi family , 457 nuclear NAD+ metabolism , 334–335 gene repression , 457–458 Index 575

Ino80 family , 456 transcription initiation Swi2/Snf2 family , 456 CHD remodelers , 111 yeast Chd1 function , 454 INO80 remodelers , 111 Chromatin remodeling ISWI remodelers , 110–111 factors , 367 SWI/SNF remodelers , 109–110 RNAPI and RNAPIII regulation , 113–114 Coactivator-associated arginine transcription methyltransferase 1 (CARM1), 433 chromatin remodelers (see Chromatin Cockayne syndrome type B (CSB) , 125 remodelers) Coffi n-Siris and Nicolaides-Baraitser nucleosomal organization, remodelers syndromes , 126 contributions , 455 Complex Proteins Associated with Set1 Chromatin remodeling complexes. See also (COMPASS) , 281 Remodelers Core histones tails and extensions DNA-DSBs repair “acidic patch” on H2A/H2B dimer , 10 ATP-dependent , 497 H3 N-terminal tails , 10–11 classifi cation , 497 N-and C-terminal extensions , 9–10 description , 496–497 CSB. See Cockayne syndrome type B (CSB) and INO80 (see INO80 chromatin CTCF. See CCCTC-binding factor (CTCF) remodeling complexes) C-terminal domain (CTD) and RSC ( see Remodels structure of kinases chromatin (RSC) complex) basal transcription factor TFIIH , 435–436 and SWI/SNF (see Sucrose non- CDK8/cyclin C pair , 436 fermenting (SNF) complexes) CDK7/cyclin H pair , 436 and SWR1 ( see SWR1 complexes) cyclin-dependent kinases (CDKs) , 435 DNA replication Kin28 function inhibition , 436 G1/S transition , 517–518 polo-like kinase (Plk3) , 436 replication fork, polymerases , 518–519 serine-2 phosphorylation , 436 sequence fi delity , 515 phosphatases before S-phase , 515–517 Fcp1, in yeast , 437 stalled replication forks , 520–521 kinase and phosphatase activities , Chromatin structure 436–437 chemical landscape , 3 RNAPII dephosphorylation , 436 DNA , 2 Rtr1, regulator of transcription 1 , 437

(H3/H4)2 tetramer , 4 Ssu72, phosphorylated serine-5 higher-order , 19–22 phosphatase, 437 histones , 3 phosphorylation and elongation factors negative stain electron microscopy , 4 recruitment nucleosome core , 2 chromatin immunoprecipitation (ChIP) Chromatosome and linker histones experiments , 438 C-terminal domain (CTD) , 19 co-transcriptional RNA processing , 439 DNA binding motifs , 19 gene expression regulation , 437–438 N-terminal domain , 19 histone-modifying enzymes , 438–439 single linker , 18 phospho-CTD interacting proteins , 438 Chromosomal processes, Remodeler functions in promoter-bound RNAPII , 438 chromosome cohesion and segregation , 103 serine-5 phosphorylated RNAPII , 438 DNA repair and recombination , 104–106 RNAPII DNA replication , 102–103 alanine residue , 433 dosage compensation , 101–102 associated proteins , 433–435 gene repression , 107–109 CARM1 , 433 large chromatin domains, insulators, heptad repeats, retention , 433 and boundaries, 100–101 mammalian , 433 promoter architectures and transitions , phosphorylation cycle , 433–434 106–107 productive transcription elongation , RNAPI and RNAPIII regulation , 113–114 433–434 transcription elongation , 112–113 variability , 433 576 Index

D H2B, mono-ubiquitylation , 265–270 Daxx histone chaperone , 469 non-histone targets DNA-double strand breaks (DSBs) repair BRCA1 , 273 chromatin remodeling complexes (see E3 ubiquitin-protein isopeptide ligases , Chromatin remodeling complexes, 273 DNA-DSBs repair) proliferating cell nuclear antigen error-prone repair and cell death , 494 (PCNA) , 273 H2A phosphorylation , 496 protein substrates , 272 HM loci , 495 Rad6 , 273 HR and RAD52 epistasis group proteins , 494 EGFR. See Epidermal growth factor receptor MAT locus , 495, 496 (EGFR) Mec1 and Tel1 amplifi cation , 496 Epidermal growth factor receptor NHEJ , 494, 495 (EGFR) , 564 S. cerevisiae , 496 E3 ubiquitin-protein isopeptide ligase , ssDNA binding protein , 494 271–272, 277–278 DNA methylation Exons and introns , 445 5hmC , 567 EZH2, H3K27 methylation , 244–245 5mC , 565, 567 DNA methylation and histone methylation in mammals F histone methylation targeting , 243 Facilitates chromatin transcription (FACT) H3K4 demethylation , 243 chaperones, 395 H3K9 methylation , 242–243 Facilitates chromatin transcription (FACT) in model organisms histone chaperone, 286 Arabidopsis thaliana , 241–242 Families of Remodeler Neurospora crassa , 241–242 CHD , 81–82 DNA repair and replication processes composition with orthologous subunits ATP-dependent chromatin remodeling and in vitro functions, 76–78 complexes , 493–494 human Remodeler subtype chromatin modifi cation strategies , 493 compositions , 79 covalent modifi cation , 494 INO80 , 82–83 DNA-DSBs repair (see DNA-double strand ISWI , 80–81 breaks (DSBs) repair) “Orphan” Remodelers , 83–84 genetic information encoded , 493 species origin , 79–80 mechanisms , 521 SWI/SNF , 83 DNA superhelix and core histone-DNA Floating-Harbor syndrome , 126 interactions Fluorescence recovery after photobleaching 146-bp palindromic DNA sequence , 11 (FRAP) , 393 crystal structures , 13 FRAP. See Fluorescence recovery after features , 13 photobleaching (FRAP) interface types , 11–12 superhelix location 0 (SHL0) , 11 TA base pairs and GC-rich sequences , 13 G DNA translocation underlies Remodeler Gene bodies , 445 mechanisms, 87–91 Genetic dissection, heterochromatin Dot1-mediated di-and tri-methylation , 282 ADE2, adenine biosynthetic pathway , Drosophila ring-associated factor (dRAF) 540–541 complex , 271 chromo domain, HP1 , 542 Drosophila RNF2-ortholog Sce , 271 chromosomal proteins , 541 D. melanogaster and S. cerevisiae , 541 eye phenotype , 540 E PEV , 540 E2/E3 enzymes, histone ubiquitylation Genomic DNA , 358 H2A, mono-ubiquitylation , 270–272 Glycosylation , 453–454 Index 577

H pericentric heterochromatin , 533–534 H2A-H2B deposition , 395 polycomb bound , 536, 538 HATs. See Histone acetyltransferases (HATs) posttranslational modifi cations , 536 H2A.Z exchange , 48–49 properties, euchromatin , 534, 535 H2A.Z-H2B deposition RNAi, heterochromatin formation , 542–544 bromodomain factor 1 (Bdf1) , 396 satellite DNA , 532 FACT complex , 395 transposable element, agouti gene , 533 relative accumulation , 395–396 Heterochromatin Protein 1a (HP1a) SWI2/SNF2-related CBP activator protein chromo domain , 536 (SRCAP) , 396 Drosophila , 541, 542 SWR1-C , 396 S. pombe , 543 Swr2 subunit , 395 SUVAR3-9 , 542 Tat-interactive protein 60 kDa (TIP60) Heterochromatin reassembly , 43 complex , 396 H3.3 exchange , 49–50 HDACs. See Histone deacetylases (HDACs) H3.1-H4 deposition Heterochromatin anti-silencing function 1 (ASF1) , 388–389 cell types , 536 Chromatin Assembly Factor-1 (CAF-1) , centromeres and telomeres , 534 387–390 classifi cation , 534, 535 DNA synthesis coupled (DSC) constitutive heterochromatin , 532 pathway , 388 cytological studies , 534 HIstone Regulator A (HIRA) , 390 disease , 546–547 model , 388–389 DNA methylation , 536–538 nuclear autoantigenic sperm protein Eaf3 bound , 536, 538 (NASP) , 390 eukaryotes , 536 pre-deposition complexes , 388 eukaryotic genomes , 532 proliferating cell nuclear antigen factors and histone modifi cations , 548 (PCNA) , 388 facultative heterochromatin , 532 Xenopus studies , 390 genetic dissection (see Genetic dissection, H3.3-H4 deposition heterochromatin) chromodomain helicase DNA-binding genomic transposition , 548 protein 1 (CHD1), 393 HP1a , 536 DAXX/ATRX complex , 393 methylation and silencing , 533 domain-associated protein (DAXX) , neuropathies , 533 391–393 nuclear organization and dynamics in Drosophila , 391 chromosomal rearrangements , 546 HIRA knockout embryonic stem (ES) ionizing radiation , 546 cells , 391 LBR , 545 histone binding domain (HBD) , 391–393 nuclear envelope , 544–545 RNA polymerase II (RNAPII) , 391 nuclear lamina , 544–545 in S. cerevisiae , 390 Rabble , 544 Xenopus egg extracts , 390 SAM , 545 X-linked nuclear protein (XNP) three-dimensional nucleus impacts , 546 complex , 391

transcriptional regulator p53 , 546 (H3-H4)2 tetramer splitting , 48 packaging (see Packaging, heterochromatin) Higher-order chromatin structure PARP-1 functions description , 19 chromosome inactivation and primary structure , 20 MacroH2A, 329–330 secondary structure , 20–22 Drosophila , 327 High-mobility group domains/proteins , gene regulation , 327 98–99 in vivo studies , 327 High-resolution nucleosome core particle nuclear NAD+ concentrations , 328 structure nucleolar function and rDNA silencing , 2.8 Å resolution structure , 4–5 328–329 DNA sequences , 5 patterns, histone modifi cations, 536, 537 H3/H4 and H2A/H2B dimers , 5 578 Index

Histone acetylation telomeric heterochromatin and gene and cellular metabolism silencing, 175 acetyl-CoA cofactor , 186–187 transcription activation and regulation , class III histone deacetylases , 187 176 neurodegenerative brain and memory transcription start site (TSS) , 174 loss , 187–188 HATs and HDACs , 151–152 replicative cellular life span , 187 histone deposition and chromatin assembly Warburg effect , 187 chaperones , 169 chromatin/nucleosome structure deacetylation , 170 H3 and H4 N-ter tails , 166 DNA synthesis , 167–168 histone N-terminal (N-ter) tails, role , 166 H3K56 acetylation mark , 169 hyperacetylation , 166 lysine acetylation, role , 168–169 lysine 16 , 167 lysines 5 and 12 , 168 nucleosome arrays , 167 nucleosome assembly protein 1 Trichostatin A , 166–167 (NAP1) , 170 types , 166 replication-coupled incorporation , 170 chromatin role , 151 Rtt109 acetyltransferase , 169–170 DNA repair yeast, H3 molecules , 168 chromatin structure modulators , 177 and human diseases, drug targets double-strand breaks (DSB) , 178–179 cancer , 183–184 genomic stability maintenance , 180 cardiovascular and infl ammatory lung HDAC1 and HDAC2 , 180 diseases, 184 MOF, MYST histone acetyltransferase , cutaneous T-cell lymphomas (CTCL) , 179 185–186 nucleotide excision repair (NER) garcinol , 185 pathway , 178 histone acetyltransferases , 183 yeast histone acetyltransferase , 180 JQ1 inhibitor , 186 enzymatic interplay, regulation MORF gene , 183 and modifi cation Pan-inhibitors , 185 cis-tail cross talk , 181–182 Rubinstein–Taybi syndrome , 184 HAT and HDAC complexes , 182–183 Tip60 levels, overexpression , 184 H3K9 residue, acetylation and writers (HATs) and erasers (HDACs), 186 methylation, 181 module readers Jun N-terminal kinase (JNK) target bromodomains ( see Bromodomains) genes , 183 double PHD fi nger domain (DPF) , 165 lysine residues, sumoylation , 181 double pleckstrin homology (PH) transcriptional response to stress , 181 domain , 165 trans-tail cross talk , 181–182 histone code , 164 gene expression, regulation Rtt106 chaperone , 165 Gcn4-dependent gene promoters , 171 reaction schemes , 151 H2A-H2B dimer , 173 writing, reading, and erasing , 152 HAT complexes localization , 171 Histone acetyltransferase NuA4 complex , 359 H2AZ enrichment , 174 Histone acetyltransferases (HATs) H2AZ variant , 173–174 acetylation enzymes , 151 HBO1, MYST-family member , 172 ACTR , 154 H3K56 acetylation, budding yeast , 175 ATAC complex , 156–157 MOF acetyltransferase , 174–175 cellular processes task , 157 nucleosome choreography , 176–177 chromatin-binding domains , 157 nucleosome-free region (NFR) , 174 classifi cation , 152–154 p300/CBP HAT , 173 GNAT-family acetyltransferase complexes, Rpd3-containing complexes , 176 composition , 155 RSC remodelers , 173 HAT-A and HAT-B , 154 specifi c HAT recruitment , 172–173 H2AX acetylation , 157–159 Index 579

H2A.Z , 159 structural analysis , 161 and histone deacetylases (HDACs) , 159 zinc dependent deacetylases , 160 human and yeast histones, acetylation Histone demethylases sites , 158 amine oxidase type lysine specifi city , 156 demethylation , 229–230 MSL complex , 157 euchromatin-heterochromatin MYST family , 154, 156 boundaries, 231 NSL complex , 157 human LSD1 homolog , 231 nuclear hormone-related proteins SRC1 , 154 LSD1 , 229–231 nuclear processes , 159, 160 Su(var) 3-3 , 231 Nut1 , 154 jumonji C dioxygenase type demethylases p300/CBP (CREB-binding protein) , 154 HeLa nuclear extracts , 232 Piccolo NuA4 , 155 H3K9 demethylation , 233 protiens, active sites , 154 H3K4me2/3 demethylation , 232–233 recombinant MOF , 156 oxidative decarboxylation , 232 Saccharomyces cerevisiae , 152 Histone dynamics, elongation Tetrahymena thermophila , 152 control TFIID subunit TAF250 , 154 chromatin hypoacetylation , 461 yeast Gcn5 protein , 154 chromatin organization maintenance , Histone chaperones 462–464 cargoes, chromatin assembly/disassembly conventional promoters , 461 related functions, 31–34 FACT-mediated exchange , 464–465 centromeric chromatin reassembly , 43–46 histone deacetylation pathways , 462 chromatin assembly and disassembly H3 K36 methylation , 460–461 during DNA repair , 53–55 nucleosomal disassembly and functional roles , 30 reassembly , 460 patches, acidic residues , 31 H2A–H2B dimers , 460 replication-dependent chromatin assembly , H3–H4 tetramers , 460 37–43, 46–50 histone turnover , 460 stepwise nucleosome assembly/ inducible genes , 459–460 disassembly , 30, 31 nucleosomal destabilization , 459 transcription-dependent chromatin RNAPII transcription complex binding , 459 disassembly and reassembly , 50–53 Histone lysine methylation signaling transport from cytoplasm to nucleus components , 220 Asf1 , 36 demethylases (see Histone demethylases) H2A-H2B , 35 epigenome and histone methylation HeLa cytosolic extraction , 36 euchromatin and heterochromatin , HSP90/HSP70 , 36 220–221 Kap121 , 36–37 H3K36 di-and trimethylation levels , Kap123 , 36 221–222 Nap1 function , 35 H4K20 dimethylation , 221 Histone deacetylases (HDACs) H3K4me1 , 221 activity , 160 H3K4me3 , 221 Ash1 and Ume6 , 162–163 H3K36me3 , 222 classes , 160–161 mouse embryonic fi broblasts (MEFs), 221 class I complexes , 162 transcription start site (TSS) , 221–222 class II, multisubunit complexes methyltransferases (see Histone lysine members, 163 methyltransferases) heterochromatin 1 (HP1) protein , 163 reader domains lysine acetylation , 151 cavity-insertion , 236 methylation-dependent mechanism , 163 discrete chromatin functional states , 233 N-CoR , 163 effects , 234 NuRD , 162 heterochromatin protein 1 (HP1) , 233–234 580 Index

Histone lysine methylation signaling (cont.) modifi cation sites , 216–217 histone methyl marks , 238–240 signaling , 217 isothermal titration calorimetry lysine methylated residues , 218 (ITC) , 236 lysine-specifi c demethylase 1A (LSD1) , methyl lysine binding domains , 235 219–220 molecular basis , 236–238 modular protein-protein interactions , plant homeodomain (PHD) fi ngers , 217–218 234–235 and neoplastic disease protein domain families , 235 H3K27 methylation and cancer , 244–245 sensing and transducing events , 233–234 metabolic state and histone surface-groove methyl lysine demethylation , 246 recognition modes, 236 NSD2, H3K36 dimethylation, and Histone lysine methyltransferases multiple myeloma, 245–246 catalysis, in S. cerevisiae , 224 PEV , 219 in humans, catalysis RNA synthesis regulation , 218 H3K4 methylation , 225 Suv39H1 and HP1, drosophila H3K9 methylation , 225 homologues , 219–220 H3K27 methylation , 226 targeting , 243 H3K36 methylation , 226–228 Histone methyl marks H3K79 methylation , 228 H3K4me3, linking H4K20 methylation , 228–229 BPTF , 239 linker histones , 229 CHD1 , 240 S -adenosyl-l-homocysteine (SAH) , 222 ING2 , 239–240 SET domain ING4 , 240 active site , 223 RAG2 , 240 Drosophila melanogaster proteins , 222 Spp1 , 240 eukaryote genomes , 223 TAF3 , 239 F/Y switch , 223 multiple binding targets , 238 SAM-dependent methyltransferase reader domain-histone tail interactions , enzymes, 223 240–241 Histone methylation Histone methyltransferase complex PRC2 , 359 AdoMet , 218 Histone phosphorylation and chromatin dynamics arginine , 246–247 folding DNA , 343 chromodomain (CD) , 219 histone H1 core histones , 216 CDK1 , 345 and DNA methylation (see DNA fl uorescence labeled mutant , 345–346 methylation) mitotic chromatin condensation , 345 DNA-templated processes , 218 mouse mammary tumor virus (MMTV) gene expression, linking evidence , 219 promoter , 346 heterochromatin protein 1 (HP1) , 219 in M-phase , 345–346 H3 K4 nucleosome and , 346 H2B ubiquitylation and , 447–448 histone H3 in higher eukaryotes , 448–449 Aurora-B , 347 on transcription , 449 chromosome condensation, initiation , 348 H3 K36 heterochromatin protein 1 (HP1) , 348 in higher eukaryotes , 452 “modifi cation cassettes” concept , 348 recognition , 451–452 premature chromosome condensation , H3 K79 347 H2B ubiquitylation , 450 serine , 347 in higher eukaryotes , 450–451 serine10 phosphorylation , 347 H3K4 demethylase , 219–220 threonine 11 , 348 H3 R2 and H3 K4 methylation , 449–450 transcriptional activation , 347 lysine and arginine histone H2A chemical structure , 215–216 BAB motif , 349 methylation marks , 216–217 Bub1 , 349–350 Index 581

in Drosophila embryos , 349 Histones H2a-SA mutant , 350 CAF1 , 520 lysine 119 , 350 chaperone , 507 modifi cation network , 351 and chromatosome , 18–19 NHK-1 , 349 displacement , 506 serine 1 , 351 DNA interactions , 493 shugoshin proteins , 350 DNA replication , 516 thr119 , 349 DNA superhelix and core histone-DNA vaccinia related kinase 1 (VRK1) , 349 interactions, 11–13 histone posttranslational modifi cations , eviction 343–344 DNA replication , 37 reader protein, histone modifi cations , 352 FACT , 38–39

Histone PTMs H2A-H2B, (H3-H4)2 tetramer removal , chromatin remodelers , 458–459 39 distribution , 443–444 MCM2-7 , 37 glycosylation , 453–454 H2A C-terminus , 496 sumoylation , 453 H2Av , 511 Histone, reading modifi cations HDACs , 501 acetyltransferase NuA4 complex , 359 N-terminal region , 493 aspects , 358–359 NuA4 histone acetyltransferase complex , chromatin factors , 359 508–509 Chromatin-Related Complexes PARP-1 functions (CRCs) , 359 and core histones , 320–322 DNA template-dependent metabolic linker histone H1 , 322–323 processes, 357 modifi cations , 323–324 Eaf3 chromo domain , 371 nonhistone protein-binding partners , eukaryotic transcription machinery , 359 332–333 features , 358 posttranslational modifi cations , 332–333 functional outcomes variants and chromatin-regulating adaptors to machineries , 368 proteins , 316 architectural proteins , 367 primary structure , 6–8 chromatin modifi ers , 368–371 secondary structure , 8–9 chromatin remodeling factors , 367 tails and extensions , 9–11 genomic DNA , 358 Histone ubiquitylation methyltransferase complex PRC2 , 359 cell cycle regulation , 300 modifi ed chromatin , 359 de-ubiquitylating enzymes modules calypso , 275 53BP1, potential PTM reader , 361 non-histone targets , 275–276 bromo domains , 360 ubH2A , 274–275 chromatin-related domains , 361 ubH2B , 273–274 chromo domains , 360 Ubp8 and Ubp10 , 274 protein-protein interactions , 360–361 USP22 activity , 274–275 PTM , 357–358 and DNA repair reading modes ATM/ATR signaling , 295–296 DNA, modifi ed nucleosomes part , at damage sites , 295 362, 364 permissive chromatin environment , 299 multiple nucleosomes , 362, 365–366 reversible response , 297–300 multiple targets , 362–363 RNF168 role , 296–297 PTM , 362–363 E2/E3 enzymes specifi city H2A, mono-ubiquitylation , 270–272 MRG15 protein , 366 H2B, mono-ubiquitylation , 265–270 nucleosome-complex interaction , 366 non-histone targets , 272–273 one-domain-one-mark recognition , mono-ubiquitylated histone H2A (ubH2A) 365–366 carboxy-terminal tails , 263 WD40 domain , 366 H2AX, DNA damage , 264 582 Index

Histone ubiquitylation (cont.) factors , 402–406 in mammalian cells , 264 genes derepression , 407 in mouse cells , 262–263 hyperacetylation , 407 site , 263–264 negative regulator , 401–402 poly-ubiquitylated histones in pericentric heterochromatin , 407 H2A and H2B , 264 in Tetrahymena thermophila , 400–401 H3 variant Cse4 , 264 in transcriptional regulation , 401, reversible post-translational modifi cation 407–408 HECT domain-containing E3 ligases, 261 histone chaperones , 382 poly-ubiquitylation , 260 H3.3, transcriptionally active chromatin protein ubiquitylation , 262 in cancer studies , 398 ubiquitin , 260–261 chromatin immunoprecipitation transcription (ChIP) , 397 ubH2B correlation (see ubH2B in Drosophila , 397–398 transcription correlation) green fl uorescent protein (GFP)-tagged , Histone variants 396–397 CenH3, functional centromeres determinant HIRA knockout mouse ES cells , 397 chromosomal missegregation and homozygous DAXX mutant mice , 398 genomic instability , 399 primordial germ cell (PGC) nuclei , chromosome segregation defects , 399 397–398 euchromatin-heterochromatin in Tetrahymena thermophila , 397 boundaries, 399 human, alignment , 381 in mammals , 399–400 MacroH2A, macrodomain signifi cance , 400 ATRX syndrome , 410 in Xenopus egg extracts , 400 leucine-zipper motif , 409 characteristics poly-ADP-ribose (PAR) polymerase 1 nucleosome core particle structure , (PARP1) protein binding , 409 384–386 pseudoautosomal/pairing region secondary and higher-order chromatin (PAR) , 410 structures, 386–387 in silencing , 409 structure infl uence PTMs , 383–384 in zebrafi sh embryos , 410 classifi cation , 377 and mammalian chaperones , 378–380 deposition, on DNA mammalian histone gene characteristics , 382 CenH3-H4 , 393–395 mammalian testis-specifi c variants H2A-H2B , 395 divison , 411 H2A.Z-H2B , 395–396 gene expression , 411 H3.1-H4 , 387–390 H2A.Bbd1 , 411–412 H3.3-H4 , 390–393 H2A.Lap2/3 , 412 H2A.X, DNA damage response inactive X chromosom (Barr body) , 411 BReast CAncer protein 1 (BRCA1) , 408 knockout models uses , 412 chromatin remodeling , 409 replacement histones , 377–382 DNA damage response (DDR) replicative histones , 377 activation , 408 Histone variants on chromatin remodeling double-strand breaks (DSBs) , 408 activities , 96–97 in male gametogenesis , 409 H3K4 demethylation , 243 p53 Binding Protein 1 (53BP1) , 408 H4K20me2, intermolecular hydrogen-bonding sex chromosomes inactivation , 409 interactions, 237 H2A.Z, multitask genomic regulator H3K9 methylation , 242–243 bivalent promoters , 407 H3K27 methylation and cancer , 244–245 in breast cancer , 408 H3 Lys4 methylation , 280–281 in chromosome segregation , 407–408 H3 Lys 79 methylation , 282 in DNA repair , 400–401 5hmC. See 5-Hydroxymethylcytosine (5hmC) in Drosophila , 400, 407 Homologous recombination (HR) dual role , 407 DNA synthesis , 501 Index 583

donor and recipient loci , 495 K genetic and cytological analysis , 495 Kinetochore protein Dam1methylation, 282–283 HML and HMR donor loci , 503 INO80 , 505 MAT DSB , 495 L NHEJ , 495, 502 Lamin B receptor (LBR) , 545 RAD52 epistasis group proteins , 494 L y s63 -linked ubiquitin chains , 297 S. cerevisiae , 514 HOTAIR. See HOX antisense intergenic RNA (HOTAIR) M HOX antisense intergenic RNA (HOTAIR) , Male-Specifi c Lethal (MSL) complex , 157 558, 561 MAPKs. See Mitogen-activated protein HP1a. See Heterochromatin Protein 1a kinases (MAPKs) (HP1a) 5mC. See 5-Methylcytosine (5mC) HR. See Homologous recombination (HR) Methylammonium group, methyl lysine , 237 H3 variants H3.3 and CENPA via editing , 5-Methylcytosine (5mC) , 565, 567 95–96 Mitogen-activated protein kinases (MAPKs) , 5-Hydroxymethylcytosine (5hmC) , 567 555–556 MOF acetyltransferase , 277 Molecular chaperone , 29 I Mre11-Rad50-Xrs2 (MRX) complex , 494, Imitation SWitch 1a (ISW1a) , 15 495, 502, 507–508 INO80 chromatin remodeling complexes MSL2, human MOF-MSL complex , 270 actin/Arp4 module , 505 Arabidopsis , 505 ATPase subunits , 504 N ATP-dependent , 503 N-CoR. See Nuclear receptor Co-Repressor bacterial RuvB , 504 (N-CoR) checkpoint pathways , 514–515 Neurospora crassa , 241–242 chromatin substrate Htz1 , 514 Noncoding RNAs (ncRNAs) conventional actin and actin-related homeotic genes , 558 proteins (Arps), 504 Igf2r gene , 558–559 DNA end processing , 505 mouse Xist, Air, and Kcnq1ot1 , 558 double-strand break repair, SWR1 , PcG complex , 559 512, 513 protein coding genes , 558 in vitro DNA binding , 504 XCI , 559 MRX complex , 507–508 Xist promoter NHEJ pathway , 514 HOTAIR , 561 Nhp10 , 505–506 PRC2 , 559–560 nonfunctional , 504 XACT , 561 phospho-H2A , 507 XCI , 559–560 Pph3-dependent dephosphorylation , 507 Noncoding transcription “primes” nucleosomes , 506 chromatin organization and transcription Rvb1 and Rvb2 , 503 initiation , 465 S. cerevisiae , 512 eukaryotic and prokaryotic transcriptomes , single-stranded DNA production , 512 466 Southern blot assay , 505 gene expression regulation , 467–468 Swr1 subunits , 504 initiation , 466–467 Taf14 protein , 506 noncoding RNAs (ncRNA) , 466 temperature-sensitive actin mutants , 505 RNAPII binding , 466 INO80 family , 82–83 Nonhomologous end-joining (NHEJ) INO80 remodelers , 111 haploid yeast , 495 ISWI family , 80–81 HR pathways (see Homologous ISWI remodelers , 110–111 recombination (HR)) 584 Index

NonSpecifi c Lethal (NSL) complex , 157 analysis, well-preserved frozen mitotic NoRC. See Nucleolar remodeling complex chromosomes, 539 (NoRC) genomic environment , 539 NSD2, H3K36 dimethylation, and multiple nucleate heterochromatin , 539 myeloma , 245–246 nucleosomes , 538–539 Nuclear NAD+ metabolism protein factors , 540 DBD domain , 328 PAR-binding motif (PBM) , 316 PAR activity , 334–335 PARG. See PAR glycohydrolase (PARG) PARylation , 321 PAR glycohydrolase (PARG) , 322, 325, 333 Nuclear receptor Co-Repressor (N-CoR) , 163 PARP-1 and ADP-ribosylation Nucleolar remodeling complex (NoRC) , 328 chromatin (see Chromatin, PARP-1 Nucleoplasmin , 29 functions) Nucleosomal patterning , 440 coregulator activity , 316, 319 Nucleosome core particle structure CTCF and insulator function , 326–327 crystallization , 17 DNA-binding transcription factors , 316 DNA accessibility , 17–18 DNA methylation , 325–326 hemisome , 17–18 family members , 314–318 hexasome and tetrasome , 17 heterochromatin (see Heterochromatin, high-resolution , 4–6 PARP-1 functions) histones ( see Histones) histone ( see Histones, PARP-1 functions) PTMs , 16–17 modulations , 316 surface and interactions structure and function , 312–313 BAH (Bromo-Associated Homology) target proteins , 313–314 domain , 15 PARylation functions H2B αC helices, 13 autoPARylation , 333 H4 N-terminal tail , 14 chromatin , 320 Imitation SWitch 1a (ISW1a) , 15 core histones , 320–321 protein domains , 15 CTCF-binding sites , 326 Nucleosome core particle (NCP) structure DNA damage , 321 CenH3-containing , 384–385 DNA hypermethylation , 325 double-variant , 386 dPARP causes , 322, 324 H2A-H2B and H2A.Z-H2B dimers , L929 fi brosarcoma cells and NIH-3T3L1 385–386 fi broblast cells , 325 high-resolution X-ray structure , 384 NAD+ promotes , 321 Holliday Junction-Recognizing Protein PARP-1 , 333 (HJURP), 385 rDNA silencing , 329 inner protein , 384 target protein activity , 313–315 stability , 385 PBAF. See Polybromo BRG1-associated factor unique chromatin organization , 384 (PBAF) Nucleosome phasing and spacing , 72–73 PBM. See PAR-binding motif (PBM) Nucleosome remodeling and deacetylation PCNA. See Proliferating cell nuclear antigen (NuRD), 162, 454 (PCNA) Nucleosomes , 29 PEV. See Position effect variegation (PEV) NuRD. See Nucleosome remodeling PHD domain , 86–87 and deacetylation (NuRD) Phosphorylation , 99 PKM2. See Pyruvate kinase M2 (PKM2) Polybromo BRG1-associated factor (PBAF), 500 O Polycomb repressive complex 1 (PRC1) , “Orphan” Remodelers , 83–84 270–271 Polymerase-Associated Factor (PAF) complex , 278–280 P Position effect variegation (PEV) Packaging, heterochromatin E(var) mutations , 541 analysis, interphase chromatin , 539 loss, silencing , 542 Index 585

phenomenon , 540 chromatin processes and Remodeler transposable element , 540 functions , 73–75 Posttranslational modifi cations (PTMs) compositional attributes shared by , 75–76 acetylation , 99–100 composition and biophysical properties, formylation , 442 nucleosomes histone core/canonical histone proteins , 70 acetylation , 445–446 eukaryotes , 71–72 glycosylation , 453–454 histone-DNA contact sites , 71 methylation (see Histone methylation) and disease syndromes , 124–126 modifi cations , 445 families and compositional specialization , sumoylation , 453 76–84 monoubiquitylation of histone H2B functions in particular chromosomal (H2Bub) , 447 processes, 100–114 PARylation , 100 mechanisms and regulation , 87–100 phosphorylation , 99, 446 nucleosome phasing and spacing concept , poly-ADP ribosylation , 446 72–73 specifi c , 442–443 in pluripotency, development and transcribed genes, anatomy differentiation, 114–121 exons and introns , 445 lineage-specifi c remodelers , 116–119 gene bodies , 445 plant development , 120–121 promoters , 443–444 Remodeler regulation of body plan , PRC1. See Polycomb repressive complex 1 119–120 (PRC1) stem cell circuitry and pluripotency , Primary structure, histones 114–116 charge disparity , 7 PTM-interacting motifs , 84–87 H3 and H4 proteins , 7 Remodels structure of chromatin (RSC) H1 C-terminal domains , 8 complex histone-fold heterodimers , 6 chromatin remodeling , 497–499 histone-fold octamer , 7 DNA DSB repair , 501–503 linker histones (H1/H5) , 8 Replication-dependent chromatin assembly ranges , 6 CenH3 , 46 Proliferating cell nuclear antigen (PCNA) , 273 destabilize nucleosomes , 47 Promoter architectures and transitions H2A.Z exchange , 48–49 closed promoters , 107 H3.3 exchange , 49–50

open promoters , 106 (H3-H4)2 tetramer splitting , 48 Promoters , 443–444 histone deposition PTMs. See Posttranslational modifi cations H2A-H2B and H1 deposition , 42–43 (PTMs) heterochromatin reassembly , 43 Pyruvate kinase M2 (PKM2) H3-H4 deposition , 40–42 EGFR , 564 utilized methods , 39–40 serine and glycine biosynthesis , 564 histone eviction , 37–39 RING fi nger domain , 296 RITS. See RNA-induced transcriptional R silencing complex (RITS) Regulatory Particle Triphosphatase RNAi, heterochromatin formation (Rpt) , 450 A. thaliana , 543 Remodeler motif utilization , 87 Dicer enzyme , 544 Remodeler PTMs , 459 drosophila , 544 Remodeler regulation of body plan , 119–120 female germline , 544 Remodelers repetitive elements , 542 and cancer RITS , 543 CHD family , 123–124 schizosaccharomyces pombe , 543 ISWI family , 123 RNA-induced transcriptional silencing SWI/SNF family , 121–123 complex (RITS) , 543 586 Index

RNA polymerase II CTD , 283 Suv39H1 and HP1, drosophila homologues , RNF20/40-interacting protein , 278 219–220 RNF168 role , 296–298 SWI/SNF family , 83 RSC complex. See Remodels structure SWI/SNF remodelers , 109–110 of chromatin (RSC) complex SWR1 complexes checkpoint pathways , 514–515 and INO80 (see INO80 chromatin S remodeling complexes) S-adenosyl methionine (SAM) , 545 SAM. See S-adenosyl methionine (SAM) SAPKs. See Stress-activated protein kinases T (SAPKs) TAR. See Transcription-associated Secondary structure recombination (TAR) chromatin Transcriptional repression, ubH2B 9 Å crystal structure, tetranucleosome , 21 2A-HUB and 2A-DUB complexes , 291 linker DNA , 20 higher order chromatin structure, linker lengths , 21 regulation , 294 30 nm fi ber , 20, 22 H3 Lys4 methylation two-start organization , 21 chromatin templates reconstitution , histones 291–292 antiparallel arrangement , 8 cytokine genes , 293 core octamer , 8 Drosophila KDM2 , 293 extensions and tails , 8–9 E3 ubiquitin ligases , 293 Silencing Mediator of Retinoic acid and MLL3-mediated tri-methylation , Thyroid hormone receptors 291–293 (SMRT) , 163 RNA polymerase II , 291–293 SIR complex, architectural proteins , 367 multiple mechanisms , 294 S M R T . See Silencing Mediator of Retinoic polycomb complex-associated repression acid and Thyroid hormone receptors gene targets and inactive X (SMRT) chromosome, 289–290 Spt-Ada-Gcn5 acetyltransferase (SAGA) Hox cluster , 288–289 transcription coactivator complex , PR-DUB complex , 289–290 273–274 RNF2, in mammals , 288–289 Stem cell circuitry and pluripotency, RNF2/Ring1-defi cient cells , 289 Remodeler involvement , 114–116 transcriptional silencing , 289 Stress-activated protein kinases (SAPKs) X inactivation, in mice , 289 Drosophila , 556 Transcription-associated recombination MAPKs , 555–556 (TAR) , 558 RSC chromatin remodeling complex , Transcription-dependent chromatin 556–557 disassembly and reassembly Sucrose non-fermenting (SNF) complexes Asf1 chromatin remodeling complexes , 499–501 deletion , 51 DNA DSB repair , 501–503 H3K56Q mutation , 51 Drosophila , 499 RNA Pol II elongation , 50–51 embryonic stem (ES) cells , 501 Rtt109, acetyltransferase activity , HDACs , 501 51–52 mammalian complexes , 500 rtt106D hir1D mutants , 52 nucleosome sliding , 500 FACT RSC complexes (see Remodels structure of H2A-H2B dimer removal , 52 chromatin (RSC) complex) H3-H4 and H2A-H2B eviction , 53 S. cerevisiae , 499–500 H3 K36 , 53 SWI/SNF activity , 499 Nhp6 , 52 WSTF-SNF2h complex , 519 RNA Pol II passage , 52 Sumoylation , 453 Spt6 , 53 Index 587

Transcription start site (TSS) , 320, 322 termination Transcription through chromatin cleavage and polyadenylation factor chromatin architecture (see Chromatin (CPF), 439 architecture) DNA helicase Sen1 and RNA-binding DNA-dependent RNA polymerase , 430 proteins , 439 elongation poly(A)-dependent , 439 initiation site sets selection , 432 RNA processing factors , 440 kinases (see C-terminal domain TSS. See Transcription start site (TSS) (CTD)) phosphatases (see C-terminal domain (CTD)) U phosphorylation and elongation factors ubH2B transcription correlation recruitment ( see C-terminal domain activation, specifi c genes , 277 (CTD)) coding regions, factors for , 283–285 promoter clearance , 432 effi cient transcription , 283 promoter-proximal transcriptional E3 ligases, transcription activators recruit , pausing , 432 277–278 reversible phosphorylation, highly expressed genes, enrichment on , CTD , 432 276–277 ribonucleotide addition , 432 H3 Lys4 methylation , 280–281 eukaryotic RNAP complexes , 430–431 H3 Lys79 methylation , 282 gene organization and transcription initiation and elongation cycle , 430 Bur1/Bur2 (BUR) cyclindependent histone dynamics, elongation protein kinase complex , 278–280 H2A–H2B dimers , 460 carboxy-terminal domain (CTD) , 280 H3–H4 tetramers , 460 Kin28 , 280 histone turnover , 460 Polymerase-Associated Factor (PAF) inducible genes , 459–460 complex , 278–280 nucleosomal destabilization , 459 steps , 279 RNAPII transcription complex kinetochore protein Dam1methylation , binding , 459 282–283 initiation nucleosome occupancy/stability , 285–286 basal transcription factors , 431 nucleosomes effect , 286–287 functional RNA production , 431 in regulation , 287–288 promoter melting , 431–432 in transcription cycle , 276 RNAPII, coding regions interaction , 432 initiation, gene promoter , 430 W noncoding transcription (see Noncoding Wolf Hirschhorn syndrome (WHS) , 245 transcription) phage SP6 polymerase , 429 polynucleosomes , 429 X preinitiation complex (PIC) formation , 431 X active chromosome transcript (XACT) , 561 PTMs ( see Posttranslational modifi cations X-chromosome inactivation (XCI) (PTMs)) dosage, X-linked genes , 559 RNAPII , 430, 431 RepA-RNA , 559 RNAPII CTD (see C-terminal domain Xact expression , 561 (CTD)) XCI. See X-chromosome inactivation (XCI)