Histone H3 Trimethylation at Lysine 36 is Associated with Constitutive and Facultative Heterochromatin

Overview

Journal Genome Res

Specialty Genetics

Date 2011 Aug 2

PMID 21803857

Citations 71

Authors

Sophie Chantalat

Arnaud Depaux

Patrick Hery

Sophie Barral

Jean-Yves Thuret

Stefan Dimitrov

Matthieu Gerard

Affiliations

Soon will be listed here.

Abstract

The mammalian genome contains numerous regions known as facultative heterochromatin, which contribute to transcriptional silencing during development and cell differentiation. We have analyzed the pattern of histone modifications associated with facultative heterochromatin within the mouse imprinted Snurf-Snrpn cluster, which is homologous to the human Prader-Willi syndrome genomic region. We show here that the maternally inherited Snurf-Snrpn 3-Mb region, which is silenced by a potent transcription repressive mechanism, is uniformly enriched in histone methylation marks usually found in constitutive heterochromatin, such as H4K20me3, H3K9me3, and H3K79me3. Strikingly, we found that trimethylated histone H3 at lysine 36 (H3K36me3), which was previously identified as a hallmark of actively transcribed regions, is deposited onto the silenced, maternally contributed 3-Mb imprinted region. We show that H3K36me3 deposition within this large heterochromatin domain does not correlate with transcription events, suggesting the existence of an alternative pathway for the deposition of this histone modification. In addition, we demonstrate that H3K36me3 is markedly enriched at the level of pericentromeric heterochromatin in mouse embryonic stem cells and fibroblasts. This result indicates that H3K36me3 is associated with both facultative and constitutive heterochromatin. Our data suggest that H3K36me3 function is not restricted to actively transcribed regions only and may contribute to the composition of heterochromatin, in combination with other histone modifications.

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References

Carrozza M, Li B, Florens L, Suganuma T, Swanson S, Lee K . Histone H3 methylation by Set2 directs deacetylation of coding regions by Rpd3S to suppress spurious intragenic transcription. Cell. 2005; 123(4):581-92. DOI: 10.1016/j.cell.2005.10.023. View

Nimura K, Ura K, Shiratori H, Ikawa M, Okabe M, Schwartz R . A histone H3 lysine 36 trimethyltransferase links Nkx2-5 to Wolf-Hirschhorn syndrome. Nature. 2009; 460(7252):287-91. DOI: 10.1038/nature08086. View

Berlivet S, Houlard M, Gerard M . Loss-of-function studies in mouse embryonic stem cells using the pHYPER shRNA plasmid vector. Methods Mol Biol. 2010; 650:85-100. DOI: 10.1007/978-1-60761-769-3_7. View

Pannetier M, Julien E, Schotta G, Tardat M, Sardet C, Jenuwein T . PR-SET7 and SUV4-20H regulate H4 lysine-20 methylation at imprinting control regions in the mouse. EMBO Rep. 2008; 9(10):998-1005. PMC: 2525564. DOI: 10.1038/embor.2008.147. View

Bannister A, Schneider R, Myers F, Thorne A, Crane-Robinson C, Kouzarides T . Spatial distribution of di- and tri-methyl lysine 36 of histone H3 at active genes. J Biol Chem. 2005; 280(18):17732-6. DOI: 10.1074/jbc.M500796200. View

Mietton F, Sengupta A, Molla A, Picchi G, Barral S, Heliot L . Weak but uniform enrichment of the histone variant macroH2A1 along the inactive X chromosome. Mol Cell Biol. 2008; 29(1):150-6. PMC: 2612491. DOI: 10.1128/MCB.00997-08. View

Jones B, Su H, Bhat A, Lei H, Bajko J, Hevi S . The histone H3K79 methyltransferase Dot1L is essential for mammalian development and heterochromatin structure. PLoS Genet. 2008; 4(9):e1000190. PMC: 2527135. DOI: 10.1371/journal.pgen.1000190. View

Rea S, Eisenhaber F, OCarroll D, Strahl B, Sun Z, Schmid M . Regulation of chromatin structure by site-specific histone H3 methyltransferases. Nature. 2000; 406(6796):593-9. DOI: 10.1038/35020506. View

Strahl B, Grant P, Briggs S, Sun Z, Bone J, Caldwell J . Set2 is a nucleosomal histone H3-selective methyltransferase that mediates transcriptional repression. Mol Cell Biol. 2002; 22(5):1298-306. PMC: 134702. DOI: 10.1128/MCB.22.5.1298-1306.2002. View

10.

Holm V, Cassidy S, Butler M, Hanchett J, Greenswag L, Whitman B . Prader-Willi syndrome: consensus diagnostic criteria. Pediatrics. 1993; 91(2):398-402. PMC: 6714046. View

11.

Landers M, Bancescu D, Le Meur E, Rougeulle C, Glatt-Deeley H, Brannan C . Regulation of the large (approximately 1000 kb) imprinted murine Ube3a antisense transcript by alternative exons upstream of Snurf/Snrpn. Nucleic Acids Res. 2004; 32(11):3480-92. PMC: 443545. DOI: 10.1093/nar/gkh670. View

12.

Humpherys D, Eggan K, Akutsu H, Hochedlinger K, Rideout 3rd W, Biniszkiewicz D . Epigenetic instability in ES cells and cloned mice. Science. 2001; 293(5527):95-7. DOI: 10.1126/science.1061402. View

13.

Trojer P, Reinberg D . Facultative heterochromatin: is there a distinctive molecular signature?. Mol Cell. 2007; 28(1):1-13. DOI: 10.1016/j.molcel.2007.09.011. View

14.

Kouzarides T . Chromatin modifications and their function. Cell. 2007; 128(4):693-705. DOI: 10.1016/j.cell.2007.02.005. View

15.

Xiao T, Hall H, Kizer K, Shibata Y, Hall M, Borchers C . Phosphorylation of RNA polymerase II CTD regulates H3 methylation in yeast. Genes Dev. 2003; 17(5):654-63. PMC: 196010. DOI: 10.1101/gad.1055503. View

16.

Shively L, Chang L, LeBon J, Liu Q, Riggs A, Singer-Sam J . Real-time PCR assay for quantitative mismatch detection. Biotechniques. 2003; 34(3):498-502, 504. DOI: 10.2144/03343st01. View

17.

Wang Z, Zang C, Rosenfeld J, Schones D, Barski A, Cuddapah S . Combinatorial patterns of histone acetylations and methylations in the human genome. Nat Genet. 2008; 40(7):897-903. PMC: 2769248. DOI: 10.1038/ng.154. View

18.

Wu M, Tsai T, Beaudet A . Deficiency of Rbbp1/Arid4a and Rbbp1l1/Arid4b alters epigenetic modifications and suppresses an imprinting defect in the PWS/AS domain. Genes Dev. 2006; 20(20):2859-70. PMC: 1619944. DOI: 10.1101/gad.1452206. View

19.

Bielinska B, Blaydes S, Buiting K, Yang T, Krajewska-Walasek M, Horsthemke B . De novo deletions of SNRPN exon 1 in early human and mouse embryos result in a paternal to maternal imprint switch. Nat Genet. 2000; 25(1):74-8. DOI: 10.1038/75629. View

20.

Sun X, Wei J, Wu X, Hu M, Wang L, Wang H . Identification and characterization of a novel human histone H3 lysine 36-specific methyltransferase. J Biol Chem. 2005; 280(42):35261-71. DOI: 10.1074/jbc.M504012200. View