DNA Methylation Patterns Expose Variations in Enhancer-chromatin Modifications During Embryonic Stem Cell Differentiation

Overview

Journal PLoS Genet

Specialty Genetics

Date 2021 Apr 12

PMID 33844685

Citations 7

Authors

Adi Alajem

Hava Roth

Sofia Ratgauzer

Danny Bavli

Alex Motzik

Shlomtzion Lahav

Itay Peled

Oren Ram

Affiliations

Soon will be listed here.

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.

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