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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Main Authors: Andrew D. King, Kevin Huang, Liudmilla Rubbi, Shuo Liu, Cun-Yu Wang, Yinsheng Wang, Matteo Pellegrini, Guoping Fan
Format: Article
Language:English
Published: Elsevier 2016-09-01
Series:Cell Reports
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2211124716311792
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author Andrew D. King
Kevin Huang
Liudmilla Rubbi
Shuo Liu
Cun-Yu Wang
Yinsheng Wang
Matteo Pellegrini
Guoping Fan
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
collection DOAJ
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.
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spelling doaj.art-3245b8381cfe4c31a3a42ec27bd453aa2022-12-22T00:24:32ZengElsevierCell 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
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
title 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_short 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
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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