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Snapshot: Chromatin Remodeling: ISWI Adam N SnapShot: Chromatin Remodeling: ISWI Adam N. Yadon and Toshio Tsukiyama Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA Saccharomyces cerevisiae Caenorhabditis elegans Trypanosoma brucei Isw2 Isw2 Isw1a Isw1b NURF ISWI Itc1 Itc1 Dls1 Ioc3 Ioc4 Ioc2 NURF1 ? Dpb4 Isw1 Isw2 Isw2 Isw1 Isw1 Isw1 Replication, transcription, and Transcription regulation2 3 4 Ty1 integration regulation1 Cell fate determination Transcription regulation Drosophila melanogaster Arabidopsis thaliana ACF CHRAC NURF RSF CHR11 CHR17 ACF1 CHRAC NURF38 ? ACF1 RSF1 15 NURF301 ? CHRAC ISWI ISWI 16 ISWI RbAp ISWI CHR11 CHR17 46/48 Nucleosome assembly, transcription, Chromatin structure and Chromatin structure and Developmental cellular 5 6 7 expansion and Functions unknown and replication regulation transcription regulation transcription regulation nuclear divisions8 Mammals Xenopus laevis ACF1 CHRAC RSF CERF ACF WICH ACF1 ACF1 CHRAC ACF1 15 RSF1 CECR2 WSTF CHRAC SNF2L SNF2H SNF2H 17 SNF2H ISWI p175 ISWI Chromatin structure and Replication and transcription regulation9 Development and Heterochromatin formation centromere maintenance10 transcription regulation11 Functions unknown and/or replication regulation12 NoRC WICH WCRF NURF ISWI-A ISWI-D p15 TIP5 WSTF WCRF180 p70 p200 BPTF p200 p21 p55 SNF2L RbAp SNF2H SNF2H SNF2H ISWI ISWI 46/48 p17 13 DNA replication and Cell differentiation and Transcription regulation repair regulation14 Functions unknown transcription regulation15 Functions unknown Functions unknown Biochemical Activities Nucleosome sliding ATP ADP ISWI Histone replacement ATP ADP Histones + General domain structure ISWI Helicase SANT DEXD ATPase HAND SLIDE 454 Cell 144, February 4, 2011 ©2011 Elsevier Inc. DOI 10.1016/j.cell.2011.01.019 See online version for legend and references SnapShot: Chromatin Remodeling: ISWI Adam N. Yadon and Toshio Tsukiyama Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA The imitation switch (ISWI) family of ATP-dependent chromatin-remodeling enzymes comprises highly conserved protein complexes that utilize the energy of ATP hydrolysis to slide nucleosomes along DNA and/or replace histones within nucleosomes. All ATP-dependent chromatin-remodeling complexes, including the ISWI family, contain a conserved catalytic DEXD ATPase domain and a helicase domain. However, the combination of three C-terminally located domains, known as HAND, SANT, and SLIDE, is unique to ISWI family members. The SANT domain (structurally related to the c-Myb DNA-binding domains) binds unmodified histone tails, the SLIDE (SANT-like ISWI domain) domain binds nucleosomal DNA near the dyad axis, and the HAND domain is implicated in both histone and DNA binding/recognition. Representative ISWI-containing protein complexes from multiple species are depicted in this SnapShot, with specific in vivo biological functions for each listed below. Biological Functions of ISWI-Containing Complexes 1. Replication, Transcription, and Ty Integration Regulation Facilitates replication fork progression through late-replicating regions; represses mRNA and cryptic noncoding RNA transcription by negatively regulating NFR size; required for the periodic integration pattern of the Ty1 retrotransposon. 2. Transcription Regulation Represses and activates transcription at a small number of loci and is implicated in transcription elongation and termination regulation. 3. Cell Fate Determination Promotes the expression of vulval cell fates by antagonizing the transcriptional and chromatin-remodeling activities of complexes similar to Myb-MuvB/dREAM, NuRD, and Tip60/NuA4. 4. Transcription Regulation Downregulates VSV expression sites. 5. Nucleosome Assembly, Transcription, and Replication Regulation Required for the establishment and/or maintenance of periodic nucleosome arrays that contributes to pericentric position-effect variegation (PEV) and heterochromatic Poly- comb-mediated transcriptional gene silencing; implicated in the regulation of S phase length/progression. 6. Chromatin Structure and Transcription Regulation Maintains higher-order chromatin structure by mediating chromatin compaction; disrupts the enhancer-blocking function of Fab7 and SF1 while augmenting the function of Fab8; activates transcription of GAGA target genes and ecdysone-responsive genes and is a coactivator of Armadillo; regulates innate immunity by repressing transcription of JAK/STAT target genes. 7. Chromatin Structure and Transcription Regulation Involved in formation of silent heterochromatin by incorporating the histone variant H2Av, thus suppressing position-effect variegation (PEV). 8. Developmental Cellular Expansion and Nuclear Divisions Necessary for cell expansion during late-diploid (sporophytic) embryogenesis and mitotic nuclear divisions during haploid (gametophytic) phase. 9. Replication and Transcription Regulation Required for S phase progression and facilitates pericentromeric heterochromatin DNA replication; represses transcription of the vitamin D3 receptor-regulated genes in humans. 10. Chromatin Structure and Centromere Maintenance Implicated in chromatin assembly and actively supports the assembly of CENP-A chromatin in humans. 11. Development and Transcription Regulation Functions in neural tube formation and terminal differentiation of ovarian granulose cells through regulation of StAR gene expression in mice. 12. Heterochromatin Formation and/or Replication Regulation Targeted to pericentromeric heterochromatin during early stages of chromosome condensation and DNA replication. 13. Transcription Regulation Involved in the transcriptional repression of ribosomal RNA genes. 14. DNA Replication and Repair Regulation Implicated in heterochromatin DNA replication by binding PCNA in mice; necessary for cell survival following DNA damage by methyl methanesulfate (MMS); and facilitates a DNA damage response pathway by controlling histone H2A.Z function in mice. 15. Cell Differentiation and Transcription Regulation Promotes neurite outgrowth and transcription of engrailed 1 and 2 in humans. ACKNOWLEDGMENTS T.T. is funded by NIGMS. A.N.Y. was supported by a Developmental Biology Predoctoral Training Grant T32HD007183 from the National Institute of Child Health and Human Develop- ment. REFERENCES Bowman, G.D. (2010). Mechanisms of ATP-dependent nucleosome sliding. Curr. Opin. Struct. Biol. 20, 73–81. Clapier, C.R., and Cairns, B.R. (2009). The biology of chromatin remodeling complexes. Annu. Rev. Biochem. 78, 273–304. Dang, W., and Bartholomew, B. (2007). Domain architecture of the catalytic subunit in the ISW2-nucleosome complex. Mol. Cell. Biol. 27, 8306–8317. Gangaraju, V.K., Prasad, P., Srour, A., Kagalwala, M.N., and Bartholomew, B. (2009). Conformational changes associated with template commitment in ATP-dependent chromatin remodeling by ISW2. Mol. Cell 35, 58–69. Whitehouse, I., Rando, O.J., Delrow, J., and Tsukiyama, T. (2007). Chromatin remodelling at promoters suppresses antisense transcription. Nature 450, 1031–1035. Yadon, A.N., Van de Mark, D., Basom, R., Delrow, J., Whitehouse, I., and Tsukiyama, T. (2010). Chromatin remodeling around nucleosome-free regions leads to repression of noncod- ing RNA transcription. Mol. Cell. Biol. 30, 5110–5122. 454.e1 Cell 144, February 4, 2011 ©2011 Elsevier Inc. DOI 10.1016/j.cell.2011.01.019 .
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