Reversible Regulation of Promoter and Enhancer Histone Landscape by DNA Methylation in Mouse Embryonic Stem Cells

Overview

Journal Cell Rep

Publisher Cell Press

Specialties Biology
Cell Biology
Molecular Biology

Date 2016 Sep 30

PMID 27681438

Citations 61

Authors

Andrew D King

Kevin Huang

Liudmilla Rubbi

Shuo Liu

Cun-Yu Wang

Yinsheng Wang

Matteo Pellegrini

Guoping Fan

Affiliations

Soon will be listed here.

Abstract

DNA methylation is one of a number of modes of epigenetic gene regulation. Here, we profile the DNA methylome, transcriptome, and global occupancy of histone modifications (H3K4me1, H3K4me3, H3K27me3, and H3K27ac) in a series of mouse embryonic stem cells (mESCs) with varying DNA methylation levels to study the effects of DNA methylation on deposition of histone modifications. We find that genome-wide DNA demethylation alters occupancy of histone modifications at both promoters and enhancers. This is reversed upon remethylation by Dnmt expression. DNA methylation promotes H3K27me3 deposition at bivalent promoters, while opposing H3K27me3 at silent promoters. DNA methylation also reversibly regulates H3K27ac and H3K27me3 at previously identified tissue-specific enhancers. These effects require DNMT catalytic activity. Collectively, our data show that DNA methylation is essential and instructive for deposition of specific histone modifications across regulatory regions, which together influences gene expression patterns in mESCs.

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References

Heintzman N, Stuart R, Hon G, Fu Y, Ching C, Hawkins R . Distinct and predictive chromatin signatures of transcriptional promoters and enhancers in the human genome. Nat Genet. 2007; 39(3):311-8. DOI: 10.1038/ng1966. View

Nili Gal-Yam E, Egger G, Iniguez L, Holster H, Einarsson S, Zhang X . Frequent switching of Polycomb repressive marks and DNA hypermethylation in the PC3 prostate cancer cell line. Proc Natl Acad Sci U S A. 2008; 105(35):12979-84. PMC: 2529074. DOI: 10.1073/pnas.0806437105. View

Zhang Y, Jurkowska R, Soeroes S, Rajavelu A, Dhayalan A, Bock I . Chromatin methylation activity of Dnmt3a and Dnmt3a/3L is guided by interaction of the ADD domain with the histone H3 tail. Nucleic Acids Res. 2010; 38(13):4246-53. PMC: 2910041. DOI: 10.1093/nar/gkq147. View

Lu F, Liu Y, Jiang L, Yamaguchi S, Zhang Y . Role of Tet proteins in enhancer activity and telomere elongation. Genes Dev. 2014; 28(19):2103-19. PMC: 4180973. DOI: 10.1101/gad.248005.114. View

Gkountela S, Zhang K, Shafiq T, Liao W, Hargan-Calvopina J, Chen P . DNA Demethylation Dynamics in the Human Prenatal Germline. Cell. 2015; 161(6):1425-36. PMC: 4458157. DOI: 10.1016/j.cell.2015.05.012. View

Fuks F, Hurd P, Wolf D, Nan X, Bird A, Kouzarides T . The methyl-CpG-binding protein MeCP2 links DNA methylation to histone methylation. J Biol Chem. 2002; 278(6):4035-40. DOI: 10.1074/jbc.M210256200. View

Reddington J, Perricone S, Nestor C, Reichmann J, Youngson N, Suzuki M . Redistribution of H3K27me3 upon DNA hypomethylation results in de-repression of Polycomb target genes. Genome Biol. 2013; 14(3):R25. PMC: 4053768. DOI: 10.1186/gb-2013-14-3-r25. View

Stadler M, Murr R, Burger L, Ivanek R, Lienert F, Scholer A . DNA-binding factors shape the mouse methylome at distal regulatory regions. Nature. 2011; 480(7378):490-5. DOI: 10.1038/nature10716. View

Shen Y, Yue F, McCleary D, Ye Z, Edsall L, Kuan S . A map of the cis-regulatory sequences in the mouse genome. Nature. 2012; 488(7409):116-20. PMC: 4041622. DOI: 10.1038/nature11243. View

10.

Feng J, Chang H, Li E, Fan G . Dynamic expression of de novo DNA methyltransferases Dnmt3a and Dnmt3b in the central nervous system. J Neurosci Res. 2005; 79(6):734-46. DOI: 10.1002/jnr.20404. View

11.

Hon G, Song C, Du T, Jin F, Selvaraj S, Lee A . 5mC oxidation by Tet2 modulates enhancer activity and timing of transcriptome reprogramming during differentiation. Mol Cell. 2014; 56(2):286-297. PMC: 4319980. DOI: 10.1016/j.molcel.2014.08.026. View

12.

Elliott G, Hong C, Xing X, Zhou X, Li D, Coarfa C . Intermediate DNA methylation is a conserved signature of genome regulation. Nat Commun. 2015; 6:6363. PMC: 4333717. DOI: 10.1038/ncomms7363. View

13.

Chen T, Ueda Y, Xie S, Li E . A novel Dnmt3a isoform produced from an alternative promoter localizes to euchromatin and its expression correlates with active de novo methylation. J Biol Chem. 2002; 277(41):38746-54. DOI: 10.1074/jbc.M205312200. View

14.

Wu H, Coskun V, Tao J, Xie W, Ge W, Yoshikawa K . Dnmt3a-dependent nonpromoter DNA methylation facilitates transcription of neurogenic genes. Science. 2010; 329(5990):444-8. PMC: 3539760. DOI: 10.1126/science.1190485. View

15.

Hon G, Rajagopal N, Shen Y, McCleary D, Yue F, Dang M . Epigenetic memory at embryonic enhancers identified in DNA methylation maps from adult mouse tissues. Nat Genet. 2013; 45(10):1198-206. PMC: 4095776. DOI: 10.1038/ng.2746. View

16.

Vire E, Brenner C, Deplus R, Blanchon L, Fraga M, Didelot C . The Polycomb group protein EZH2 directly controls DNA methylation. Nature. 2005; 439(7078):871-4. DOI: 10.1038/nature04431. View

17.

Yoon H, Chan D, Reynolds A, Qin J, Wong J . N-CoR mediates DNA methylation-dependent repression through a methyl CpG binding protein Kaiso. Mol Cell. 2003; 12(3):723-34. DOI: 10.1016/j.molcel.2003.08.008. View

18.

Xie W, Schultz M, Lister R, Hou Z, Rajagopal N, Ray P . Epigenomic analysis of multilineage differentiation of human embryonic stem cells. Cell. 2013; 153(5):1134-48. PMC: 3786220. DOI: 10.1016/j.cell.2013.04.022. View

19.

Cedar H, Bergman Y . Linking DNA methylation and histone modification: patterns and paradigms. Nat Rev Genet. 2009; 10(5):295-304. DOI: 10.1038/nrg2540. View

20.

Cooper S, Dienstbier M, Hassan R, Schermelleh L, Sharif J, Blackledge N . Targeting polycomb to pericentric heterochromatin in embryonic stem cells reveals a role for H2AK119u1 in PRC2 recruitment. Cell Rep. 2014; 7(5):1456-1470. PMC: 4062935. DOI: 10.1016/j.celrep.2014.04.012. View