Reversible Regulation of Promoter and Enhancer Histone Landscape by DNA Methylation in Mouse Embryonic Stem Cells
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...
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doaj-3245b8381cfe4c31a3a42ec27bd453aa2020-11-25T01:31:30ZengElsevierCell Reports2211-12472016-09-0117128930210.1016/j.celrep.2016.08.083Reversible Regulation of Promoter and Enhancer Histone Landscape by DNA Methylation in Mouse Embryonic Stem CellsAndrew D. King0Kevin Huang1Liudmilla Rubbi2Shuo Liu3Cun-Yu Wang4Yinsheng Wang5Matteo Pellegrini6Guoping Fan7Department of Human Genetics and Broad Stem Cell Research Center, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 90095, USADepartment of Human Genetics and Broad Stem Cell Research Center, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 90095, USADepartment of Molecular, Cell, and Developmental Biology, University of California Los Angeles, Los Angeles, CA 90095, USADepartment of Chemistry, University of California Riverside, Riverside, CA 92521, USADivision of Oral Biology and Medicine, School of Dentistry, University of California Los Angeles, Los Angeles, CA 90095, USADepartment of Chemistry, University of California Riverside, Riverside, CA 92521, USADepartment of Molecular, Cell, and Developmental Biology, University of California Los Angeles, Los Angeles, CA 90095, USADepartment of Human Genetics and Broad Stem Cell Research Center, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 90095, USADNA 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.http://www.sciencedirect.com/science/article/pii/S2211124716311792DNA methylationhistone modificationschromatinpolycombembryonic stem cellsenhancerspromotersgene regulationepigenetics |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Andrew D. King Kevin Huang Liudmilla Rubbi Shuo Liu Cun-Yu Wang Yinsheng Wang Matteo Pellegrini Guoping Fan |
spellingShingle |
Andrew D. King Kevin Huang Liudmilla Rubbi Shuo Liu Cun-Yu Wang Yinsheng Wang Matteo Pellegrini Guoping Fan Reversible Regulation of Promoter and Enhancer Histone Landscape by DNA Methylation in Mouse Embryonic Stem Cells Cell Reports DNA methylation histone modifications chromatin polycomb embryonic stem cells enhancers promoters gene regulation epigenetics |
author_facet |
Andrew D. King Kevin Huang Liudmilla Rubbi Shuo Liu Cun-Yu Wang Yinsheng Wang Matteo Pellegrini Guoping Fan |
author_sort |
Andrew D. King |
title |
Reversible Regulation of Promoter and Enhancer Histone Landscape by DNA Methylation in Mouse Embryonic Stem Cells |
title_short |
Reversible Regulation of Promoter and Enhancer Histone Landscape by DNA Methylation in Mouse Embryonic Stem Cells |
title_full |
Reversible Regulation of Promoter and Enhancer Histone Landscape by DNA Methylation in Mouse Embryonic Stem Cells |
title_fullStr |
Reversible Regulation of Promoter and Enhancer Histone Landscape by DNA Methylation in Mouse Embryonic Stem Cells |
title_full_unstemmed |
Reversible Regulation of Promoter and Enhancer Histone Landscape by DNA Methylation in Mouse Embryonic Stem Cells |
title_sort |
reversible regulation of promoter and enhancer histone landscape by dna methylation in mouse embryonic stem cells |
publisher |
Elsevier |
series |
Cell Reports |
issn |
2211-1247 |
publishDate |
2016-09-01 |
description |
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. |
topic |
DNA methylation histone modifications chromatin polycomb embryonic stem cells enhancers promoters gene regulation epigenetics |
url |
http://www.sciencedirect.com/science/article/pii/S2211124716311792 |
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