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PERSPECTIVE

Chromatin-based transcriptional punctuation

Paul B. Talbert1 and Steven Henikoff Howard Hughes Medical Institute, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA

The long polycistronic units of trypano- motifs for initiation and termination of transcription, somes do not appear to be demarcated by the usual DNA which suggests a very different strategy for transcrip- motifs that punctuate transcription in familiar eukar- tional regulation from what is found in more familiar yotes. In this issue of Genes & Development, Siegel and organisms, including animals, fungi, and . These ob- colleagues (pp. 1063–1076) describe a system for the de- servations have led to the notion that a different system is marcation of trypanosome transcription units based on responsible for transcriptional regulation (Clayton 2002). the deposition and turnover of variants rather As described by Siegel et al. (2009) in this issue of Genes than on the binding of transcription factors. Replication- & Development, the punctuation of transcription appears independent incorporation of histone variants and de- to be governed by the incorporation of histone variants. stabilization of is an emerging theme at This discovery has important implications for more famil- promoters of more familiar , and it now iar organisms, where histone variant incorporation has appears that this system is an evolutionarily conserved taken a back seat to DNA-binding proteins in specifying mode of transcriptional punctuation. where transcription starts and stops.

Trypanosome histone variants and transcription Eukaryotes have evolved remarkably diverse cellular takes place in the context of forms encoded by genomes that are regulated by a com- nucleosomes that wrap DNA, thereby achieving a greater mon set of chromatin proteins. Studies that catalog the compaction of the genome while restricting access of diversity of mechanisms for eukaryotic gene expression the transcriptional machinery. The bulk of nucleosomes focus on only a few well-studied model organisms, and are composed of octamers of two molecules each of the ‘‘from yeast to man’’ is a phrase that is often used to four ‘‘canonical’’ core —H3, H4, H2B, and H2A— indicate generality in eukaryotic biology. However, our which are among the most highly conserved proteins in favorite model organisms thrive in man-made environ- eukaryotes. Each of these histones, however, also exists ments, and only when a ‘‘freaky’’ has an impact in variant forms that can carry out specialized functions. on human health or wealth does it become a popular Functionally distinct variants are uncommon for H4 and organism for intensive study. In this regard, trypano- H2B but are universal, or nearly so, for H3 and H2A somes belong to a highly distinctive eukaryotic lineage (Malik and Henikoff 2003). Considerable work in yeast that has become a model organism because of its enor- and multicellular eukaryotes in recent years has estab- mous impact on human health. They are well-known to lished the common functions that are mediated by us because of the human misery they cause as blood- nucleosomes bearing H3 and H2A variants. H3.3 medi- borne parasites, including brucei, which ates replacement and marks active chroma- causes African sleeping sickness that is transmitted by tin (Waterborg 1993; Ahmad and Henikoff 2002), CenH3 tsetse flies, and others that cause Chagas’ disease and functions in chromosome segregation (Amor et al. 2004), leishmaniasis. H2A.X participates in DNA repair (Loizou et al. 2006), The intensive study of trypanosome biology aimed at and H2AZ is associated with promoters (Raisner et al. dealing with these scourges has also uncovered remark- 2005) and maintains accessible chromatin that prevents able features of their genomic organization and chroma- silencing in yeast (Meneghini et al. 2003) and DNA tin biology. Notably, gene transcription is polycistronic, methylation in plants (Zilberman et al. 2008). Histone with 59 and 39 ends that appear to lack the usual sequence variants in unicellular , however, do not fit so neatly into these common functional categories. No- [Keywords: ; histone variants; histone modification; where has this been more of a puzzle than in trypano- genome-wide ChIP-seq; transcription initiation; transcription termination] 1Corresponding author. somes. Trypanosomes have two forms of each of the four E-MAIL [email protected]; FAX (206) 667-5889. histones, all of which are considerably diverged from the Article is online at http://www.genesdev.org/cgi/doi/10.1101/gad.1806409. Freely available online through the Genes & Development Open Access canonical histones of plants and animals (Alsford and option. Horn 2004; Siegel et al. 2009).

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Talbert and Henikoff

The two forms of H2A in T. brucei are markedly divergent from other H2As but appear to correspond to the canonical H2A and its universal variant, H2AZ. Previous work has shown that T. brucei H2AZ is co- incident in distribution and specifically coimmunopreci- pitates with the H2B variant H2BV, with which it is presumed to dimerize (Lowell et al. 2005). H2BV has only 38% identity to its more conventional H2B counterpart and, together with H2AZ, it is required for viability, indicating that H2AZ/H2BV nucleosomes have a func- tion distinct from H2A/H2B nucleosomes. Siegel et al. (2009) describe a previously uncharacter- Figure 1. Schematic diagram of a portion of a T. brucei chro- ized variant of H4 in T. brucei, designated H4V, which is mosome. Polycistronic transcription of co-oriented protein- 85% identical to its H4 counterpart. The unusual occur- coding genes occurs from divergent SSRs and terminates at rence of variants of H4 and H2B in trypanosomes is convergent SSRs, which are often inhabited by tRNA genes. striking, but no less so than the complement of only Incorporation of H2AZ/H2BV/H3K4me/H4K10ac nucleosomes two forms of H3 variants, both highly divergent from occurs at putative transcription initiation sites and incorpora- tion of H2A/H2B/H3V/H4V nucleosomes occurs at putative canonical H3. Multicellular eukaryotes commonly have transcription termination sites (Clayton 2002; Mandava et al. three forms of H3. In addition to the canonical form that 2008; Siegel et al. 2009). is incorporated exclusively during replication, a nearly identical variant known as H3.3 incorporates in replace- ment nucleosomes that are assembled throughout the some genomes, however, lack recognizable pol II pro- cell cycle, including during replication (Ahmad and moter elements (Clayton 2002). General transcription Henikoff 2002). H3.3 is incorporated after transcription factors that act on protein-encoding genes have been (Schwartz and Ahmad 2005) and is enriched at the 59 end difficult to find, and most known families of locus- of genes and also in regulatory elements, where nucleo- specific transcription factors appear to be absent from some remodeling complexes may be responsible for its the genome (Iyer et al. 2008). turnover (Henikoff 2008). Although the replication- In order to gain insight into whether chromatin struc- dependent H3 is commonly called canonical, ascomycetes ture and histone variants play a role in transcription such as yeast and some unicellular organisms such as the initiation, Siegel et al. (2009) used chromatin immuno- Cyanidioschyzon and Chlamydomonas have only precipitation (ChIP) to tagged or untagged histone var- a single form of packaging H3 that corresponds function- iants or modifications followed by Solexa sequencing of ally to replication-independent H3.3. Replication-specific the nucleosomal DNA (ChIP-seq) to map the locations of forms of canonical H3 appear to have evolved recurrently histone variants on the assembled genome sequence. in eukaryotic evolution, presumably by divergence from Using an antibody to H4 acetylated on Lys 10 (H4K10ac), H3.3-like forms (Waterborg and Robertson 1996; Malik they found twin peaks of H4K10ac enrichment at every and Henikoff 2003). A third near-universal but much less SSR with divergently oriented transcription units, and no conserved H3 variant, called CENP-A or CenH3, specifies peaks at convergent SSRs. They also found 61 single the centromere and is essential for kinetochore assembly peaks not at SSRs, most of which were downstream from (Amor et al. 2004). The two T. brucei H3s, designated H3 pol III-transcribed tRNA genes that interrupted what and H3V, are ;60% identical. Neither variant corre- otherwise appeared to be a single polycistronic pol II sponds to replication-coupled H3 nor, surprisingly, to transcription unit. All but three other tRNA genes were CenH3, which is missing from trypanosome genomes found in convergent SSRs, leading Siegel et al. (2009) to (Lowell and Cross 2004). propose that all peaks of H4K10ac enrichment correspond Trypanosomes are highly unusual for eukaryotes in to transcription start sites either at divergent SSRs or be- having polycistronic transcription units of up to 100 tween adjacent co-oriented transcription units, many of genes, similar to bacterial except that cotran- which terminate at sites associated with pol III-transcribed scribed genes are not generally functionally related tRNA genes. Comparing the positions of these putative (Fig. 1). mRNAs are separated post-transcriptionally by transcription start sites between procyclic and blood- coupled reactions that polyadenylate and splice a 39- stream forms of the parasite, they found only one unique nucleotide (nt) leader onto every mRNA (Liang et al. peak in each form. Antibodies against tagged H2AZ and 2003). Neighboring transcription units can be either H2BV gave peaks of enrichment coincident with anti- convergent or divergent, and the regions between them H4K10ac, suggesting that transcription start sites are are known as strand switch regions (SSRs). Nuclear run- characterized by nucleosomes containing H2AZ, H2BV, on assays in the related trypanosomatids and H4K10ac. Previous studies showed that H2BV- major and , which are highly syntenic containing nucleosomes are enriched in trimethylated with T. brucei (El-Sayed et al. 2005), showed that RNA H3K4 (Mandava et al. 2008) and that divergent SSRs are polymerase II (pol II) transcription initiates at diver- also enriched with acetylated H3 (Respuela et al. 2008). gent SSRs and terminates at convergent SSRs (Martinez- Acetylation of histone tails has been thought to in- Calvillo et al. 2003, 2004; Respuela et al. 2008). Trypano- crease nucleosome mobility by neutralizing the charged

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Transcriptional punctuation by chromatin lysines that help mediate interactions with DNA and nucleosomes are incorporated following pol III transcrip- other histones (Waterborg 2002). Nucleosomes contain- tion. These and other ideas are ripe for testing, starting ing H2AZ have also been shown to be less stable than with careful transcript mapping and further investigation H2A nucleosomes when in nucleosome core particles of the structures and properties of variant nucleosomes. with H3.3 (Jin and Felsenfeld 2007). This raises the possibility that less stable nucleosomes at transcription Evolution of eukaryotic transcriptional punctuation start sites of trypanosomes facilitate transcription initia- tion. To test this possibility, Siegel et al. (2009) used Are trypanosomes just evolutionary freaks, or do they antibodies against equivalently tagged versions of H2AZ offer a window into the evolution of transcription and and H2A or H2BV and H2B and compared the ability of histone variants in eukaryotes? Phylogenetic trees of each tagged histone to coimmunoprecipitate H3 and H4 small subunit ribosomal RNA initially led to the view after washing chromatin pellets in increasing concentra- that trypanosomes, their relatives, and a handful tions of salt. They found significantly less association of of protists lacking mitochondria are very early-branching H3 and H4 with tagged H2AZ and H2BV, consistent with eukaryotes, in contrast to the ‘‘crown’’ eukaryotes that H2AZ/H2BV nucleosomes being less stable. include plants, animals, fungi, and numerous other pro- Besides modifying nucleosome mobility, acetylated tist groups (Sogin and Silberman 1998). However, early lysines on histones can serve as binding sites for bromo- branching in these trees has been claimed to be an artifact proteins. Siegel et al. (2009) investigated such of systematic errors in tree construction methods, espe- proteins and found one, BDF3, that colocalized cytolog- cially long branch attraction, and one ‘‘early-branching’’ ically with H4K10ac. ChIP-seq profiles showed that group, the Microsporidia, was shown to be related to BDF3 overlapped H4K10ac peaks and was concentrated fungi (Hirt et al. 1999). Improved methods and additional over the 59 ends of transcription units. Siegel et al (2009) data have not succeeded in relating other early-branching also analyzed the DNA sequences of the putative tran- groups to ‘‘crown’’ groups, but most other early-branching scription start sites and found them enriched in runs of eukaryotes including trypanosomes have been proposed nine to 15 consecutive guanines. to belong to the , a group defined by cytoskeletal The distribution of tagged versions of variants H3V and features mostly related to the flagellar apparatus, and by H4V was also investigated. H3V was known previously to molecular phylogenies (Simpson 2003). The monophyly be localized at telomeric/subtelomeric sites (Lowell and of excavates has been difficult to verify (Simpson 2003; Cross 2004). ChIP-seq confirmed this distribution, but Yoon et al. 2008) but appears to be gaining support also revealed tagged H3V at convergent SSRs and up- (Rodriguez-Ezpeleta et al. 2007; Hampl et al. 2009). The stream of single non-SSR H4K10ac peaks, the sites of position of excavates such as trypanosomes relative to presumed pol II transcription termination. Tagged H4V the root of the eukaryotic tree and whether they are truly coincided with H3V at presumed termination sites, but early branching, however, remain controversial (Rodriguez- showed less enrichment over telomeric and subtelomeric Ezpeleta et al. 2007; Hampl et al. 2009) and, therefore, so regions. is the notion that their transcriptional peculiarities, Siegel et al. (2009) propose a model of transcriptional including the lack of recognizable elements initiation in which H3K4 methylation is needed for and transcription initiation factors, might preserve an- H4K10 acetylation, which would serve as a binding site cestral characteristics. for BDF3. In turn, BDF3 would recruit transcription Transcriptional regulation in other putative excavates factors or complexes involved in such as the lamblia and the para- incorporating H2AZ/H2BV dimers into nucleosomes. basalid vaginalis differs from trypano- The less stable H2AZ/H2BV/H3K4me/H4K10ac nucleo- somes, lacking polycistronic messages and trans-spliced somes are proposed to be permissive for polymerase leaders, but has other unusual, putatively primitive binding and transcription initiation. The nearly complete features (Vanacova et al. 2003). Whereas metazoans have acetylation of H4K10 at all putative transcription start heterogeneous promoters that combine diverse gene- sites argues against a role in regulating transcription specific enhancers with common shared promoter ele- levels. Instead, mRNA levels appear to be regulated ments such as the TATA-box and initiator element, post-transcriptionally (Clayton 2002). Runs of Gs may Giardia has simple compact promoters generally occu- confer directionality on transcription, either through pying <70 base pairs (bp) and including a short upstream direct effects on polymerase processivity or through TATA-like element and an initiator element, both of DNA-binding factors. H2A/H2B/H3V/H4V nucleosomes which lack any highly conserved sequence beyond AT mark sites of pol II transcription termination and often richness (Vanacova et al. 2003; Teodorovic et al. 2007). coincide with tRNA genes. Yeast tRNA genes are clus- These promoters function bidirectionally, with the tered and their subnuclear localization can inhibit pol II TATA-like and initiator elements apparently switching transcription (Kendall et al. 2000), and Siegel et al. (2009) roles, producing an abundance of noncoding antisense suggest that a similar clustering process in T. brucei transcripts. Transcripts also can be produced from AT- could lead to an island of pol III transcription from which rich patches (cryptic promoters) throughout the genome pol II is effectively excluded. An alternative model is that (Teodorovic et al. 2007), suggesting a rather promiscuous H3V/H4V-containing nucleosomes have increased stabil- mode of transcriptional initiation. The three Giardia ity and are not easily traversed by pol II. Perhaps these RNA polymerases have most of the standard subunits

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Talbert and Henikoff found in polymerases from crown eukaryotes but lack closely resemble canonical H2A or H2AZ but must have those subunits specific to just one of the polymerases and the general packaging function of H2A and also has the have only four of 12 general transcription initiation peptide sequence necessary to serve as an H2A.X (Malik factors, which suggests that the missing factors evolved and Henikoff 2003). In yeast, promoters are marked by after the divergence of Giardia from the lineage of the nucleosome depletion around the transcription initiation crown group (Best et al. 2004). Trichomonas has pro- site that is bound by a Myb-related DNA-binding protein moters with a simple highly conserved initiator element and by flanking H2AZ nucleosomes (Raisner et al. 2005). and additional small upstream gene-specific elements In Giardia, promoters occupy <70 bp, and the average (Liston and Johnson 1999; Vanacova et al. 2003). The space between genes is only 372 bp, or about two initiator sequence is bound by a unique protein, IBP39, nucleosomes. Are these intergenic spaces kept depleted that interacts with the C-terminal domain (CTD) of the of nucleosomes by DNA-binding proteins or, if not, how largest subunit of pol II (Lau et al. 2006). IBP39 is without are the nucleosomes mobilized to allow transcription? known homologs in other eukaryotes, suggesting that The apparent punctuation of transcription by histone Trichomonas also diverged from the main line of eukary- variant incorporation and turnover seen in trypanosomes otic descent before general transcription factors became parallels an emerging theme in transcriptional regulation sophisticated and fixed in their roles. Consistent with of more familiar eukaryotes, where these processes occur this scenario, the DNA-binding domain of IBP39 has in the context of regulation of transcription by nonhis- given rise to a family of >100 putative transcription tone DNA-binding proteins. DNA elements can bind factors in Trichomonas (Iyer et al. 2008). proteins or position nucleosomes, histone variants can In plants, animals, and fungi, the CTD of the largest produce nucleosomes of different stabilities, and modifi- subunit of pol II is composed of numerous heptad repeats cations to histone tails can further stabilize or destabilize of YSPTSPS and functions in several processes in tran- nucleosomes both by affecting their interaction with scription, including transcriptional elongation and pre- DNA and by binding proteins that help anchor or remodel mRNA processing. These heptad repeats are absent from nucleosomes (Henikoff 2008). This toolkit of nuclear the CTDs of Giardia, Trichomonas, and trypanosomes proteins has been employed differently to regulate tran- and are reduced and divergent in a fourth putative scription in different organisms, and some processes, excavate, the free-living heterolobosean amoeboflagellate such as turnover of nucleosomes at regulatory sequences gruberi (Dacks et al. 2002; Stiller and Hall upstream of promoters, have become necessary innova- 2002). Investigation into the evolution of the pol II largest tions as transcription itself evolved in complexity. Lack- subunit (RPB1) led to the proposal that heptad repeats ing sophisticated regulatory sequences, trypanosomes may have been ancestral for eukaryotes but did not appear to have innovated the deployment of histone become essential and fixed in sequence until a later time, variants to achieve transcriptional regulation. Early- when increased sophistication of CTD functions led to branching eukaryotes, even if some of them turn out to more intricate patterns of gene expression and splicing be derived rather than primitive, offer a window into the that made possible a ‘‘CTD’’ clade of developmentally evolutionary plasticity and constancy of methods of complex eukaryotes (Stiller and Hall 2002). achieving gene expression in the context of nucleosome packaging. To the extent that they reflect ancestral conditions, they also give clues to the sequence of events Histone variants reconsidered that gave rise to the sophisticated gene regulation in Siegel et al. (2009) provide evidence that the seemingly multicellular organisms today. unregulated transcription of trypanosomes is directed by histone variants, and that transcription initiation is References effected by unstable nucleosomes containing H2AZ/ H2BV and acetylated H4, and terminated by nucleosomes Ahmad, K. and Henikoff, S. 2002. The histone variant H3.3 marks active chromatin by replication-independent nucleo- containing H3Vand H4V. Do other early-branching exca- some assembly. Mol. Cell 9: 1191–1200. vates also employ unusual histone variants to regulate Alsford, S. and Horn, D. 2004. Trypanosomatid histones. Mol. transcription? The answer is not known, but it is in- Microbiol. 53: 365–372. teresting to note that Giardia, Trichomonas, and Naegle- Amor, D.J., Kalitsis, P., Sumer, H., and Choo, K.H. 2004. ria all encode divergent H3 variants in addition to Building the centromere: From foundation proteins to 3D somewhat more conventional H3s and putative or con- organization. Trends Cell Biol. 14: 359–368. firmed (Dawson et al. 2007) CenH3s. In Giardia, the Best, A.A., Morrison, H.G., McArthur, A.G., Sogin, M.L., and variant H3B is found in numerous punctate dots on Olsen, G.J. 2004. Evolution of eukaryotic transcription: metaphase chromosomes, and does not much overlap Insights from the genome of Giardia lamblia. Genome Res. signal from antibodies to mono- and dimethylated H3K4, 14: 1537–1547. Clayton, C.E. 2002. Life without transcriptional control? From which are also present in relatively few punctate dots fly to man and back again. EMBO J. 21: 1881–1888. (Dawson et al. 2007). This pattern does not immediately Dacks, J.B., Marinets, A., Ford Doolittle, W., Cavalier-Smith, T., suggest a general role in gene transcription, and H3B was and Logsdon Jr., J.M. 2002. Analyses of RNA polymerase II proposed to have a role in nonpericentric heterochroma- genes from free-living protists: Phylogeny, long branch at- tin. ChIP-seq technology would likely clarify its role. traction, and the eukaryotic big bang. Mol. Biol. Evol. 19: Giardia has only a single form of H2A that does not 830–840.

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Transcriptional punctuation by chromatin

Dawson, S.C., Sagolla, M.S., and Cande, W.Z. 2007. The cenH3 Raisner, R.M., Hartley, P.D., Meneghini, M.D., Bao, M.Z., Liu, histone variant defines centromeres in Giardia intestinalis. C.L., Schreiber, S.L., Rando, O.J., and Madhani, H.D. 2005. Chromosoma 116: 175–184. Histone variant H2A.Z marks the 59 ends of both active and El-Sayed, N.M., Myler, P.J., Blandin, G., Berriman, M., Crabtree, inactive genes in euchromatin. Cell 123: 233–248. J., Aggarwal, G., Caler, E., Renauld, H., Worthey, E.A., Hertz- Respuela, P., Ferella, M., Rada-Iglesias, A., and Aslund, L. 2008. Fowler, C., et al. 2005. Comparative genomics of trypanoso- Histone acetylation and methylation at sites initiating di- matid parasitic . Science 309: 404–409. vergent polycistronic transcription in Trypanosoma cruzi. J. Hampl, V., Hug, L., Leigh, J.W., Dacks, J.B., Lang, B.F., Simpson, Biol. Chem. 283: 15884–15892. A.G., and Roger, A.J. 2009. Phylogenomic analyses support Rodriguez-Ezpeleta, N., Brinkmann, H., Burger, G., Roger, A.J., the monophyly of Excavata and resolve relationships among Gray, M.W., Philippe, H., and Lang, B.F. 2007. Toward re- eukaryotic ‘supergroups.’ Proc. Natl. Acad. Sci. 106: 3859–3864. solving the eukaryotic tree: The phylogenetic positions of Henikoff, S. 2008. Nucleosome destabilization in the epigenetic and cercozoans. Curr. Biol. 17: 1420–1425. regulation of gene expression. Nat. Rev. Genet. 9: 15–26. Schwartz, B.E. and Ahmad, K. 2005. Transcriptional activation Hirt,R.P.,LogsdonJr.,J.M.,Healy,B.,Dorey,M.W.,Doolittle, triggers deposition and removal of the histone variant H3.3. W.F., and Embley, T.M. 1999. Microsporidia are related to Genes & Dev. 19: 804–814. fungi: Evidence from the largest subunit of RNA poly- Siegel, T.N., Hekstra, D.R., Kemp, L.E., Figueiredo, L.M., Lowell, merase II and other proteins. Proc. Natl. Acad. Sci. 96: J.E., Fenyo, D., Wang, X., Dewell, S., and Cross, G.A.M. 2009. 580–585. Four histone variants mark the boundaries of polycistronic Iyer, L.M., Anantharaman, V., Wolf, M.Y., and Aravind, L. 2008. transcription units in Trypanosoma brucei. Genes Dev. (this Comparative genomics of transcription factors and chroma- issue). doi: 10.1101/gad.1790409. tin proteins in parasitic protists and other eukaryotes. Int. J. Simpson, A.G. 2003. Cytoskeletal organization, phylogenetic Parasitol. 38: 1–31. affinities and systematics in the contentious taxon Excavata Jin, C. and Felsenfeld, G. 2007. Nucleosome stability mediated (Eukaryota). Int. J. Syst. Evol. Microbiol. 53: 1759–1777. by histone variants H3.3 and H2A.Z. Genes & Dev. 21: 1519– Sogin, M.L. and Silberman, J.D. 1998. Evolution of the protists 1529. and protistan parasites from the perspective of molecular Kendall, A., Hull, M.W., Bertrand, E., Good, P.D., Singer, R.H., systematics. Int. J. Parasitol. 28: 11–20. and Engelke, D.R. 2000. A CBF5 mutation that disrupts Stiller, J.W. and Hall, B.D. 2002. Evolution of the RNA poly- nucleolar localization of early tRNA biosynthesis in yeast merase II C-terminal domain. Proc. Natl. Acad. Sci. 99: also suppresses tRNA gene-mediated transcriptional silenc- 6091–6096. ing. Proc. Natl. Acad. Sci. 97: 13108–13113. Teodorovic, S., Walls, C.D., and Elmendorf, H.G. 2007. Bidirec- Lau, A.O., Smith, A.J., Brown, M.T., and Johnson, P.J. 2006. tional transcription is an inherent feature of Giardia lamblia Trichomonas vaginalis initiator binding protein (IBP39) and promoters and contributes to an abundance of sterile anti- RNA polymerase II large subunit carboxy terminal domain sense transcripts throughout the genome. Nucleic Acids Res. interaction. Mol. Biochem. Parasitol. 150: 56–62. 35: 2544–2553. Liang, X.H., Haritan, A., Uliel, S., and Michaeli, S. 2003. Trans Vanacova, S., Liston, D.R., Tachezy, J., and Johnson, P.J. 2003. and cis splicing in trypanosomatids: Mechanism, factors, and Molecular biology of the amitochondriate parasites, Giardia regulation. Eukaryot. Cell 2: 830–840. intestinalis, Entamoeba histolytica and Trichomonas vagi- Liston, D.R. and Johnson, P.J. 1999. Analysis of a ubiquitous nalis. Int. J. Parasitol. 33: 235–255. promoter element in a primitive eukaryote: Early evolution Waterborg, J.H. 1993. Histone synthesis and turnover in alfalfa. of the initiator element. Mol. Cell. Biol. 19: 2380–2388. Fast loss of highly acetylated replacement histone variant Loizou, J.I., Murr, R., Finkbeiner, M.G., Sawan, C., Wang, Z.Q., H3.2. J. Biol. Chem. 268: 4912–4917. and Herceg, Z. 2006. Epigenetic information in chromatin: Waterborg, J.H. 2002. Dynamics of histone acetylation in vivo. A The code of entry for DNA repair. Cell Cycle 5: 696–701. function for acetylation turnover? Biochem. Cell Biol. 80: Lowell, J.E. and Cross, G.A. 2004. A variant histone H3 is 363–378. enriched at telomeres in Trypanosoma brucei. J. Cell Sci. Waterborg, J.H. and Robertson, A.J. 1996. Common features of 117: 5937–5947. analogous replacement histone H3 genes in animals and Lowell, J.E., Kaiser, F., Janzen, C.J., and Cross, G.A. 2005. plants. J. Mol. Evol. 43: 194–206. Histone H2AZ dimerizes with a novel variant H2B and is Yoon, H.S., Grant, J., Tekle, Y.I., Wu, M., Chaon, B.C., Cole, J.C., enriched at repetitive DNA in Trypanosoma brucei. J. Cell Logsdon Jr., J.M., Patterson, D.J., Bhattacharya, D., and Katz, Sci. 118: 5721–5730. L.A. 2008. Broadly sampled multigene trees of eukaryotes. Malik, H.S. and Henikoff, S. 2003. Phylogenomics of the BMC Evol. Biol. 8: 14. doi: 10.1186/1471-2148-8-14. nucleosome. Nat. Struct. Biol. 10: 882–891. Zilberman, D., Coleman-Derr, D., Ballinger, T., and Henikoff, S. Mandava, V., Janzen, C.J., and Cross, G.A. 2008. Trypanosome 2008. Histone H2A.Z and DNA methylation are mutually H2Bv replaces H2B in nucleosomes enriched for H3 K4 and antagonistic chromatin marks. Nature 456: 125–129. K76 trimethylation. Biochem. Biophys. Res. Commun. 368: 846–851. Martinez-Calvillo, S., Yan, S., Nguyen, D., Fox, M., Stuart, K., and Myler, P.J. 2003. Transcription of Leishmania major Friedlin chromosome 1 initiates in both directions within a single region. Mol. Cell 11: 1291–1299. Martinez-Calvillo, S., Nguyen, D., Stuart, K., and Myler, P.J. 2004. Transcription initiation and termination on Leish- mania major chromosome 3. Eukaryot. Cell 3: 506–517. Meneghini, M.D., Wu, M., and Madhani, H.D. 2003. Conserved histone variant H2A.Z protects euchromatin from the ec- topic spread of silent heterochromatin. Cell 112: 725–736.

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Chromatin-based transcriptional punctuation

Paul B. Talbert and Steven Henikoff

Genes Dev. 2009, 23: Access the most recent version at doi:10.1101/gad.1806409

Related Content Four histone variants mark the boundaries of polycistronic transcription units in Trypanosoma brucei T. Nicolai Siegel, Doeke R. Hekstra, Louise E. Kemp, et al. Genes Dev. May , 2009 23: 1063-1076

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