In:
PLOS Genetics, Public Library of Science (PLoS), Vol. 17, No. 4 ( 2021-4-12), p. e1009498-
Abstract:
In mammals, cellular identity is defined through strict regulation of chromatin modifications and DNA methylation that control gene expression. Methylation of cytosines at CpG sites in the genome is mainly associated with suppression; however, the reason for enhancer-specific methylation is not fully understood. We used sequential ChIP-bisulfite-sequencing for H3K4me1 and H3K27ac histone marks. By collecting data from the same genomic region, we identified enhancers differentially methylated between these two marks. We observed a global gain of CpG methylation primarily in H3K4me1-marked nucleosomes during mouse embryonic stem cell differentiation. This gain occurred largely in enhancer regions that regulate genes critical for differentiation. The higher levels of DNA methylation in H3K4me1- versus H3K27ac-marked enhancers, despite it being the same genomic region, indicates cellular heterogeneity of enhancer states. Analysis of single-cell RNA-seq profiles demonstrated that this heterogeneity correlates with gene expression during differentiation. Furthermore, heterogeneity of enhancer methylation correlates with transcription start site methylation. Our results provide insights into enhancer-based functional variation in complex biological systems.
Type of Medium:
Online Resource
ISSN:
1553-7404
DOI:
10.1371/journal.pgen.1009498
DOI:
10.1371/journal.pgen.1009498.g001
DOI:
10.1371/journal.pgen.1009498.g002
DOI:
10.1371/journal.pgen.1009498.g003
DOI:
10.1371/journal.pgen.1009498.g004
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10.1371/journal.pgen.1009498.g005
DOI:
10.1371/journal.pgen.1009498.t001
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10.1371/journal.pgen.1009498.s001
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10.1371/journal.pgen.1009498.s002
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10.1371/journal.pgen.1009498.s003
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10.1371/journal.pgen.1009498.s004
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10.1371/journal.pgen.1009498.s005
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10.1371/journal.pgen.1009498.s006
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10.1371/journal.pgen.1009498.s007
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10.1371/journal.pgen.1009498.s008
DOI:
10.1371/journal.pgen.1009498.s009
DOI:
10.1371/journal.pgen.1009498.s010
DOI:
10.1371/journal.pgen.1009498.s011
DOI:
10.1371/journal.pgen.1009498.s012
DOI:
10.1371/journal.pgen.1009498.s013
DOI:
10.1371/journal.pgen.1009498.s014
DOI:
10.1371/journal.pgen.1009498.s015
DOI:
10.1371/journal.pgen.1009498.s016
DOI:
10.1371/journal.pgen.1009498.s017
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2021
detail.hit.zdb_id:
2186725-2
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