Recent highlights of RNA-polymerase-II-mediated transcription

Current Opinion in Cell Biology

Volumn 16, Issue 3, 2004, Pages 263-271

  Sims III, Robert J ^a   Mandal, Subhrangsu S ^a   Reinberg, Danny ^a  

^a RUTGERS ROBERT WOOD JOHNSON MEDICAL SCHOOL   (United States)

Author keywords

DRB sensitivity inducing factor; DSIF; facilitates chromatin transcription; FACT; HIRA; histone methyltransferase; histone regulatory homolog A; HMTase; negative elongation factor; NELF; P TEFb; positive transcription elongation factor; RNA polymerase II; RNAP II

Indexed keywords

ELONGATION FACTOR; HISTONE; MESSENGER RNA; RNA POLYMERASE II; SERINE; SMALL NUCLEAR RNA;

ACETYLATION; ADENOSINE DIPHOSPHATE RIBOSYLATION; CHROMATIN STRUCTURE; CYTOPLASM; DIMERIZATION; DNA REPLICATION; ENZYME MECHANISM; ENZYME STRUCTURE; GENE CONTROL; GENE INSERTION; GENE INTERACTION; GENETIC TRANSCRIPTION; GLYCOSYLATION; INTRON; MESSENGER RNA SYNTHESIS; METHYLATION; MUTANT; NUCLEOSOME; PHOSPHORYLATION; PRIORITY JOURNAL; PROTEIN FUNCTION; REVIEW; RNA SYNTHESIS; TRANSCRIPTION REGULATION;

ANIMALS; CHROMATIN; HISTONES; HUMANS; NUCLEOSOMES; RNA POLYMERASE II; RNA, MESSENGER; TRANSCRIPTION, GENETIC; TRANSCRIPTIONAL ELONGATION FACTORS;

INSERTION SEQUENCES;

EID: 2342465953     PISSN: 09550674     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.ceb.2004.04.004     Document Type: Review

References (83)

1. Woychik N.A., Hampsey M. The RNA polymerase II machinery: structure illuminates function. Cell. 108:2002;453-463
2. Kettenberger H., Armache K.J., Cramer P. Architecture of the RNA polymerase II-TFIIS complex and implications for mRNA cleavage. Cell. 114:2003;347-357
3. Ebright R.H. RNA polymerase: structural similarities between bacterial RNA polymerase and eukaryotic RNA polymerase II. J Mol Biol. 304:2000;687-698
4. Chung W.H., Craighead J.L., Chang W.H., Ezeokonkwo C., Bareket-Samish A., Kornberg R.D., Asturias F.J. RNA polymerase II/TFIIF structure and conserved organization of the initiation complex. Mol Cell. 12:2003;1003-1013
5. Reese J.C. Basal transcription factors. Curr Opin Genet Dev. 13:2003;114-118
6. Orphanides G., Reinberg D. A unified theory of gene expression. Cell. 108:2002;439-451
7. Ni Z., Schwartz B.E., Werner J., Suarez J.R., Lis J.T. Coordination of transcription, RNA processing, and surveillance by P-TEFb kinase on heat shock genes. Mol Cell. 13:2004;55-65
8. Ahn S.H., Kim M., Buratowski S. Phosphorylation of Serine 2 within the RNA Polymerase II C-terminal domain couples transcription and 3′ end processing. Mol Cell. 13:2004;67-76 In this study, the authors demonstrate that the Ser2 CTD kinase Ctk1 is not essential for the proper association of the transcribing RNAP II with elongation factors. However, Ctk1 was shown to mediate polyadenylation factor recruitment to the end of genes. These studies implicate Ctk1, and thus Ser2 CTD phosphorylation, in productive 3′-end processing.
9. Cho H., Kim T.K., Mancebo H., Lane W.S., Flores O., Reinberg D. A protein phosphatase functions to recycle RNA polymerase II. Genes Dev. 13:1999;1540-1552
10. Ganem C., Devaux F., Torchet C., Jacq C., Quevillon-Cheruel S., Labesse G., Facca C., Faye G. Ssu72 is a phosphatase essential for transcription termination of snoRNAs and specific mRNAs in yeast. EMBO J. 22:2003;1588-1598 This study demonstrates that Ssu72 has the ability to function as a phosphatase and interacts with Kin28, an RNAP II CTD kinase, and displays functional association with Fcp1, a CTD phosphatase. Further analysis in vivo revealed that Ssu72 participates in transcription termination of select mRNAs.
11. Meinhart A., Silberzahn T., Cramer P. The mRNA transcription/processing factor Ssu72 is a potential tyrosine phosphatase. J Biol Chem. 278:2003;15917-15921
12. Yeo M., Lin P.S., Dahmus M.E., Gill G.N. A novel RNA polymerase II C-terminal domain phosphatase that preferentially dephosphorylates serine 5. J Biol Chem. 278:2003;26078-26085
13. Sun Z.W., Hampsey M. Synthetic enhancement of a TFIIB defect by a mutation in SSU72, an essential yeast gene encoding a novel protein that affects transcription start site selection in vivo. Mol Cell Biol. 16:1996;1557-1566
14. Gavin A.C., Bosche M., Krause R., Grandi P., Marzioch M., Bauer A., Schultz J., Rick J.M., Michon A.M., Cruciat C.M., et al. Functional organization of the yeast proteome by systematic analysis of protein complexes. Nature. 415:2002;141-147
15. Shilatifard A., Conaway R.C., Conaway J.W. The RNA polymerase II elongation complex. Annu Rev Biochem. 72:2003;693-715
16. Hartzog G.A. Transcription elongation by RNA polymerase II. Curr Opin Genet Dev. 13:2003;119-126
17. Arndt K.M., Kane C.M. Running with RNA polymerase: eukaryotic transcript elongation. Trends Genet. 19:2003;543-550
18. Mandal S.S., Cho H., Kim S., Cabane K., Reinberg D. FCP1, a phosphatase specific for the heptapeptide repeat of the largest subunit of RNA polymerase II, stimulates transcription elongation. Mol Cell Biol. 22:2002;7543-7552
19. Choi C.H., Hiromura M., Usheva A. Transcription factor IIB acetylates itself to regulate transcription. Nature. 424:2003;965-969 For the first time, the authors identify that the general transcription factor TFIIB can function as an auto-acetyltransferase. The auto-acetylation of TFIIB stabilizes its interaction with TFIIF and was shown to facilitate transcription in vitro and in vivo.
20. Proudfoot N.J., Furger A., Dye M.J. Integrating mRNA processing with transcription. Cell. 108:2002;501-512
21. Lindstrom D.L., Squazzo S.L., Muster N., Burckin T.A., Wachter K.C., Emigh C.A., McCleery J.A., Yates J.R. III, Hartzog G.A. Dual roles for Spt5 in pre-mRNA processing and transcription elongation revealed by identification of Spt5-associated proteins. Mol Cell Biol. 23:2003;1368-1378
22. Pei Y., Shuman S. Interactions between fission yeast mRNA capping enzymes and elongation factor Spt5. J Biol Chem. 277:2002;19639-19648
23. Pei Y., Schwer B., Shuman S. Interactions between fission yeast Cdk9, its cyclin partner Pch1, and mRNA capping enzyme Pct1 suggest an elongation checkpoint for mRNA quality control. J Biol Chem. 278:2003;7180-7188 In this paper, the authors demonstrate a novel functional interaction between capping enzyme and P-TEFb. Genetic evidence is presented that suggests Cdk9 and Pch1 in S. pombe are the functional orthologs of Bur1/Bur2, an RNAP II CTD kinase in S. cerevisiae.
24. Wen Y., Shathin A.J. Transcription elongation factor hSPT5 stimulates mRNA capping. Genes Dev. 13:1999;1774-1779
25. Chiu Y.L., Ho C.K., Saha N., Schwer B., Shuman S., Rana T.M. Tat stimulates cotranscriptional capping of HIV mRNA. Mol Cell. 10:2002;585-597
26. Mandal SS, Chu C, Wada T, Handa H, Shatkin A, Reinberg D: Functional interactions between mRNA capping enzyme and factors that positively and negatively regulate transcription during promoter escape. Proc Natl Acad Sci USA 2004, in press.
27. Moteki S., Price D. Functional coupling of capping and transcription of mRNA. Mol Cell. 10:2002;599-609
28. Pei Y., Hausmann S., Ho C.K., Schwer B., Shuman S. The length, phosphorylation state, and primary structure of the RNA polymerase II carboxyl-terminal domain dictate interactions with mRNA capping enzymes. J Biol Chem. 276:2001;28075-28082
29. Kwak Y.T., Guo J., Prajapati S., Park K.J., Surabhi R.M., Miller B., Gehrig P., Gaynor R.B. Methylation of SPT5 regulates its interaction with RNA polymerase II and transcriptional elongation properties. Mol Cell. 11:2003;1055-1066
30. Jurica M.S., Moore M.J. Pre-mRNA splicing: awash in a sea of proteins. Mol Cell. 12:2003;5-14
31. Reed R. Coupling transcription, splicing and mRNA export. Curr Opin Cell Biol. 15:2003;326-331
32. Furger A., O'Sullivan J.M., Binnie A., Lee B.A., Proudfoot N.J. Promoter proximal splice sites enhance transcription. Genes Dev. 16:2002;2792-2799
33. Kwek K.Y., Murphy S., Furger A., Thomas B., O'Gorman W., Kimura H., Proudfoot N.J., Akoulitchev A. U1 snRNA associates with TFIIH and regulates transcriptional initiation. Nat Struct Biol. 9:2002;800-805 In this study, the authors identify that the splicing factor U1 snRNA is a component of the TFIIH complex. Moreover, the U1 snRNA is shown to be important in stimulating transcription re-initiation. These studies demonstrate that snRNAs are components of transcriptional complexes and functionally regulate transcription.
34. Yik J.H., Chen R., Nishimura R., Jennings J.L., Link A.J., Zhou Q. Inhibition of P-TEFb (CDK9/Cyclin T) kinase and RNA polymerase II transcription by the coordinated actions of HEXIM1 and 7SK snRNA. Mol Cell. 12:2003;971-982
35. Andrulis E.D., Werner J., Nazarian A., Erdjument-Bromage H., Tempst P., Lis J.T. The RNA-processing exosome is linked to elongating RNA polymerase II in Drosophila. Nature. 420:2002;837-841
36. Strasser K., Masuda S., Mason P., Pfannstiel J., Oppizzi M., Rodriguez-Navarro S., Rondon A.G., Aguilera A., Struhl K., Reed R., et al. TREX is a conserved complex coupling transcription with messenger RNA export. Nature. 417:2002;304-308
37. Rondon A.G., Jimeno S., Garcia-Rubio M., Aguilera A. Molecular evidence that the eukaryotic THO/TREX complex is required for efficient transcription elongation. J Biol Chem. 278:2003;39037-39043
38. Ferdous A., Gonzalez F., Sun L., Kodadek T., Johnston S.A. The 19S regulatory particle of the proteasome is required for efficient transcription elongation by RNA polymerase II. Mol Cell. 7:2001;981-991
39. Gonzalez F., Delahodde A., Kodadek T., Johnston S.A. Recruitment of a 19S proteasome subcomplex to an activated promoter. Science. 296:2002;548-550
40. Reid G., Hubner M.R., Metivier R., Brand H., Denger S., Manu D., Beaudouin J., Ellenberg J., Gannon F. Cyclic, proteasome-mediated turnover of unliganded and liganded ERα on responsive promoters is an integral feature of estrogen signaling. Mol Cell. 11:2003;695-707
41. Narlikar G.J., Fan H.Y., Kingston R.E. Cooperation between complexes that regulate chromatin structure and transcription. Cell. 108:2002;475-487
42. Morillon A., Karabetsou N., O'Sullivan J., Kent N., Proudfoot N., Mellor J. Isw1 chromatin remodeling ATPase coordinates transcription elongation and termination by RNA polymerase II. Cell. 115:2003;425-435 This paper identifies a connection between the chromatin remodeling enzyme Isw1p and different stages of transcription. The transcription cycle is shown to be successively regulated by different forms of Isw1p, clearly implicating Isw1p as an important mediator of distinct steps during active transcription.
43. Orphanides G., LeRoy G., Chang C.H., Luse D.S., Reinberg D. FACT, a factor that facilitates transcript elongation through nucleosomes. Cell. 92:1998;105-116
44. Belotserkovskaya R., Oh S., Bondarenko V.A., Orphanides G., Studitsky V.M., Reinberg D. FACT facilitates transcription-dependent nucleosome alteration. Science. 301:2003;1090-1093 In this study, the FACT complex is demonstrated to mediate the removal of one histone H2A-H2B dimer as the RNAP II traverses a nucleosome. Additionally, FACT itself is identified to contain histone chaperone activity by facilitating histone deposition onto DNA. This work suggests a putative mechanism for maintaining the positioning of epigenetic information despite RNAP-II-mediated disruption of nucleosomes during transcription.
45. Saunders A., Werner J., Andrulis E.D., Nakayama T., Hirose S., Reinberg D., Lis J.T. Tracking FACT and the RNA polymerase II elongation complex through chromatin in vivo. Science. 301:2003;1094-1096 Chromatin immunoprecipitation and comparative immunofluorescence studies in Drosophila identify that FACT co-localizes with RNAP II on active genes. FACT recruitment upon heat shock was comparable to RNAP II, as well as the transcription elongation factors Spt5 and Spt6. This work provides important evidence that FACT functions to facilitate transcription elongation in vivo.
46. Mason P.B., Struhl K. The FACT complex travels with elongating RNA polymerase II and is important for the fidelity of transcriptional initiation in vivo. Mol Cell Biol. 23:2003;8323-8333 Chromatin immunoprecipitation studies in yeast identify that FACT associates with elongating RNAP II within the coding region of active genes. FACT is further demonstrated to be important in the maintenance of proper transcription initiation at the promoter region of genes. These studies suggest that FACT integrates initiation and elongation events to faithfully allow productive transcription.
47. Orphanides G., Reinberg D. RNA polymerase II elongation through chromatin. Nature. 407:2000;471-475
48. Wu C.H., Yamaguchi Y., Benjamin L.R., Horvat-Gordon M., Washinsky J., Enerly E., Larsson J., Lambertsson A., Handa H., Gilmour D. NELF and DSIF cause promoter proximal pausing on the hsp70 promoter in Drosophila. Genes Dev. 17:2003;1402-1414
49. Endou M, Hasegawa J, Watanabe H, Kim D-K, Aida M, Inukai N, Narita T, Shima D, Yamada T, Furuya A et al.: Spt6 stimulates in vitro transcription elongation mediated by RNA polymerase II. Mol Cell Biol 2004, in press.
50. Bortvin A., Winston F. Evidence that Spt6p controls chromatin structure by a direct interaction with histones. Science. 272:1996;1473-1476
51. Kaplan C.D., Laprade L., Winston F. Transcription elongation factors repress transcription initiation from cryptic sites. Science. 301:2003;1096-1099 This study describes the importance of Spt6 in maintaining normal chromatin architecture during transcription. Atypical transcription initiation is observed within the coding regions of genes in Spt6 mutant yeast. Further, the Spt6 mutant displays disrupted chromatin structure and underscores the importance of normal chromatin-mediated transcriptional repression of promoter regions.
52. Simic R., Lindstrom D.L., Tran H.G., Roinick K.L., Costa P.J., Johnson A.D., Hartzog G.A., Arndt K.M. Chromatin remodeling protein Chd1 interacts with transcription elongation factors and localizes to transcribed genes. EMBO J. 22:2003;1846-1856
53. Vaquero A., Loyola A., Reinberg D. The constantly changing face of chromatin. Sci Aging Knowledge Environ. 1:2003;RE4
54. Lachner M., O'Sullivan R.J., Jenuwein T. An epigenetic road map for histone lysine methylation. J Cell Sci. 116:2003;2117-2124
55. Zhang Y. Transcriptional regulation by histone ubiquitination and deubiquitination. Genes Dev. 17:2003;2733-2740
56. Sims R.J. III, Nishioka K., Reinberg D. Histone lysine methylation: a signature for chromatin function. Trends Genet. 19:2003;629-639
57. Briggs S.D., Xiao T., Sun Z.W., Caldwell J.A., Shabanowitz J., Hunt D.F., Allis C.D., Strahl B.D. Gene silencing: trans-histone regulatory pathway in chromatin. Nature. 418:2002;498
58. Dover J., Schneider J., Tawiah-Boateng M.A., Wood A., Dean K., Johnston M., Shilatifard A. Methylation of histone H3 by COMPASS requires ubiquitination of histone H2B by Rad6. J Biol Chem. 277:2002;28368-28371
59. Sun Z.W., Allis C.D. Ubiquitination of histone H2B regulates H3 methylation and gene silencing in yeast. Nature. 418:2002;104-108 In this study, the authors demonstrate the inter-dependence between ubiquitination of histone H2B-K123 and histone H3-K4 methylation in yeast. H2B-K123 ubiquitination is shown to be a prerequisite for H3-K4 methylation and important for proper telomeric silencing. This work corroborates the idea that distinct histone modifications functionally interact.
60. Ng H.H., Xu R.M., Zhang Y., Struhl K. Ubiquitination of histone H2B by Rad6 is required for efficient Dot1-mediated methylation of histone H3 lysine 79. J Biol Chem. 277:2002;34655-34657
61. Wood A., Krogan N.J., Dover J., Schneider J., Heidt J., Boateng M.A., Dean K., Golshani A., Zhang Y., Greenblatt J.F., et al. Bre1, an E3 ubiquitin ligase required for recruitment and substrate selection of Rad6 at a promoter. Mol Cell. 11:2003;267-274
62. Wood A., Schneider J., Dover J., Johnston M., Shilatifard A. The Paf1 complex is essential for histone monoubiquitination by the Rad6-Bre1 complex, which signals for histone methylation by COMPASS and Dot1p. J Biol Chem. 278:2003;34739-34742
63. Henry K.W., Wyce A., Lo W.S., Duggan L.J., Emre N.C., Kao C.F., Pillus L., Shilatifard A., Osley M.A., Berger S.L. Transcriptional activation via sequential histone H2B ubiquitylation and deubiquitylation, mediated by SAGA-associated Ubp8. Genes Dev. 17:2003;2648-2663 Here, the authors identify that both histone H2B mono-ubiquitylation and its subsequent deubiquitylation are involved in gene activation. The Ubp8 component of the SAGA acetyltransferase complex is shown to be essential for H2B de-ubiquitination. It was further observed that H2B ubiquitylation/de- ubiquitylation is an important mediator of histone H3-K4 and H3-K36 methylation, and may be a regulatory switch for productive transcription.
64. Ng H.H., Robert F., Young R.A., Struhl K. Targeted recruitment of Set1 histone methylase by elongating Pol II provides a localized mark and memory of recent transcriptional activity. Mol Cell. 11:2003;709-719 In yeast, the histone H3-K4 methyltransferase Set1 is demonstrated to be recruited by RNAP II transcription elongation factors to the 5′ end of active genes. Set1 is shown to associate exclusively with the serine-5-phosphorylated form of the RNAP II CTD. Additionally, histone H3-K4 hypermethylation is observed to persist for some time after Set1 disassociation and transcription termination.
65. Ng H.H., Dole S., Struhl K. The Rtf1 component of the Paf1 transcriptional elongation complex is required for ubiquitination of histone H2B. J Biol Chem. 278:2003;33625-33628
66. Krogan N.J., Dover J., Wood A., Schneider J., Heidt J., Boateng M.A., Dean K., Ryan O.W., Golshani A., Johnston M., et al. The Paf1 complex is required for histone H3 methylation by COMPASS and Dot1p: linking transcriptional elongation to histone methylation. Mol Cell. 11:2003;721-729 In this report, the Paf1 elongation complex was shown to be required for histone H3-K4 and H3-K79 methylation. Subunits of the Paf1 complex were demonstrated to interact directly with components of the Set1-containing histone methyltransferase complex. Importantly, this study directly links histone methylation with transcriptional elongation.
67. Li B., Howe L., Anderson S., Yates J.R. III, Workman J.L. The Set2 histone methyltransferase functions through the phosphorylated carboxyl-terminal domain of RNA polymerase II. J Biol Chem. 278:2003;8897-8903
68. Krogan N.J., Kim M., Tong A., Golshani A., Cagney G., Canadien V., Richards D.P., Beattie B.K., Emili A., Boone C., et al. Methylation of histone H3 by Set2 in Saccharomyces cerevisiae is linked to transcriptional elongation by RNA polymerase II. Mol Cell Biol. 23:2003;4207-4218 This study demonstrates that the H3-K36-specific histone methyltransferase Set2 co-purifies with RNAP II, and both Set2 and H3-K36 methylation is associated with the coding regions of active genes. The genetic interactions of Set2 identifies associations with elongation factors including the Paf1 elongation complex and Chd1, as well as H2B ubiquitination complex components. This report directly implicates histone H3-K36 methylation in transcription elongation events.
69. Xiao T., Hall H., Kizer K.O., Shibata Y., Hall M.C., Borchers C.H., Strahl B.D. Phosphorylation of RNA polymerase II CTD regulates H3 methylation in yeast. Genes Dev. 17:2003;654-663
70. Saccani S., Natoli G. Dynamic changes in histone H3 Lys 9 methylation occurring at tightly regulated inducible inflammatory genes. Genes Dev. 16:2002;2219-2224
71. Im H., Park C., Feng Q., Johnson K.D., Kiekhaefer C.M., Choi K., Zhang Y., Bresnick E.H. Dynamic regulation of histone H3 methylated at lysine 79 within a tissue-specific chromatin domain. J Biol Chem. 278:2003;18346-18352
72. Nicolas E., Roumillac C., Trouche D. Balance between acetylation and methylation of histone H3 lysine 9 on the E2F-responsive dihydrofolate reductase promoter. Mol Cell Biol. 23:2003;1614-1622
73. Martinowich K., Hattori D., Wu H., Fouse S., He F., Hu Y., Fan G., Sun Y.E. DNA methylation-related chromatin remodeling in activity-dependent BDNF gene regulation. Science. 302:2003;890-893
74. Bruno M., Flaus A., Stockdale C., Rencurel C., Ferreira H., Owen-Hughes T. Histone H2A/H2B dimer exchange by ATP-dependent chromatin remodeling activities. Mol Cell. 12:2003;1599-1606 Here, the authors describe ATP-dependent exchange of H2A/H2B within nucleosomes by the yeast SWI/SNF and RSC complexes. These complexes facilitate the re-positioning of nucleosomes to allow greater DNA accessibility, specifically by the loss of DNA-histone contacts. These results demonstrate novel activities for the SWI/SNF and RSC complexes, which were not previously believed to disrupt the histone octamer.
75. Boyer L.A., Shao X., Ebright R.H., Peterson C.L. Roles of the histone H2A-H2B dimers and the (H3-H4)(2) tetramer in nucleosome remodeling by the SWI-SNF complex. J Biol Chem. 275:2000;11545-11552
76. Mizuguchi G., Shen X., Landry J., Wu W.H., Sen S., Wu C. ATP-driven exchange of histone H2AZ variant catalyzed by SWR1 chromatin remodeling complex. Science. 303:2004;343-348 This report identifies a novel histone-exchange activity for ATP-dependent chromatin remodeling factors. The Swr1 ATPase is found to be the catalytic component of a multi-subunit complex that facilitates the exchange of H2A with the H2AZ histone variant in vitro and in vivo.
77. Krogan N.J., Keogh M.C., Datta N., Sawa C., Ryan O.W., Ding H., Haw R.A., Pootoolal J., Tong A., Canadien V., Richards D.P., Wu X., Emili A., Hughes T.R., Buratowski S., Greenblatt J.F. A Snf2 family ATPase complex required for recruitment of the histone H2A variant Htz1. Mol Cell. 12:2003;1565-1576 Through genetic interactions, a multi-subunit complex containing the Swr1 ATPase, termed SWR-C, is identified to mediate deposition of the Htz1 (H2AZ) histone variant. The SWR-C complex is demonstrated to facilitate transcription near heterochromatic regions.
78. Ahmad K., Henikoff S. The histone variant H3.3 marks active chromatin by replication-independent nucleosome assembly. Mol Cell. 9:2002;1191-1200 In this study, the authors describe the deposition of the histone H3.3 variant at distinct locations, specifically in a replication-independent manner. Replication-independent deposition does not require amino-terminal histone tails, whereas the amino-terminal tails of histone H3 are obligatory for replication-dependent deposition. These studies identify a putative mechanism for the reversal of stable, repressive histone modifications in the absence of DNA replication.
79. van Leeuwen F., Gottschling D.E. The histone minority report: the variant shall not be silenced. Cell. 112:2003;591-593
80. Meneghini M.D., Wu M., Madhani H.D. Conserved histone variant H2A.Z protects euchromatin from the ectopic spread of silent heterochromatin. Cell. 112:2003;725-736 Microarray analysis, genetic studies and chromatin immunoprecipitation assays are used to demonstrate that the histone variant H2AZ (yeast Htz1) antagonizes heterochromatin spreading and helps to establish heterochromatic boundaries. Genes activated by Htz1 are found to be located near telomeres, and reduced expression of genes in cells lacking Htz1 was reversed by mutations in the Sir2 repressor. Additionally, Sir2 and Sir3 spread inappropriately into euchromatic regions in Htz1 negative cells.
81. Tagami H., Ray-Gallet D., Almouzni G., Nakatani Y. Histone H3.1 and H3.3 complexes mediate nucleosome assembly pathways dependent or independent of DNA synthesis. Cell. 116:2004;51-61 In this report, two distinct histone chaperone complexes are identified that mediate the deposition of the H3.1 and H3.3 histone variants. Complexes containing the CAF-1 and HIRA histone chaperones are shown to facilitate DNA-synthesis-dependent and -independent deposition of H3.1 and H3.3, respectively. Further, the authors provide evidence that the H3 variants exist as H3/H4 dimers, an observation demonstrated for the first time.
82. McKittrick E, Gafken PR, Ahmad K, Henikoff S: Histone H3.3 is enriched in covalent modifications associated with active chromatin. Proc Natl Acad Sci USA 2004, in press.
83. Schneider R., Bannister A.J., Kouzarides T. Unsafe SETs: histone lysine methyltransferases and cancer. Trends Biochem Sci. 27:2002;396-402