5-hydroxymethylcytosine represses the activity of enhancers in embryonic stem cells: a new epigenetic signature for gene regulation

BMC Genomics
Inchan ChoiKyoung-Jae Won

Abstract

Recent mapping of 5-hydroxymethylcytosine (5hmC) provides a genome-wide view of the distribution of this important chromatin mark. However, the role of 5hmC in specific regulatory regions is not clear, especially at enhancers. We found a group of distal transcription factor binding sites highly enriched for 5-hdroxymethylcytosine (5hmC), but lacking any known activating histone marks and being depleted for nascent transcripts, suggesting a repressive role for 5hmC in mouse embryonic stem cells (mESCs). 5-formylcytosine (5fC), which is known to mark poised enhancers where H3K4me1 is enriched, is also observed at these sites. Furthermore, the 5hmC levels were inversely correlated with RNA polymerase II (PolII) occupancy in mESCs as well as in fully differentiated adipocytes. Interestingly, activating H3K4me1/2 histone marks were enriched at these sites when the associated genes become activated following lineage specification. These putative enhancers were shown to be functional in embryonic stem cells when unmethylated. Together, these data suggest that 5hmC suppresses the activity of this group of enhancers, which we termed "silenced enhancers". Our findings indicate that 5hmC has a repressive role at specific proximal and dist...Continue Reading

Citations

Feb 9, 2016·Cell Reports·Georgia Rose KaferPeter Mark Carlton
Oct 6, 2017·Antioxidants & Redox Signaling·Charlotte D C C van der HeijdenSamuel T Keating
Jan 20, 2018·Cell and Tissue Research·Kaat Durinck, Frank Speleman
Nov 20, 2016·Genes & Development·Rinho KimKlaus H Kaestner
Sep 22, 2017·Environmental Health Perspectives·Andres CardenasAndrea A Baccarelli
May 28, 2016·Circulation Research·Samuel T KeatingAssam El-Osta
May 6, 2020·Nucleic Acids Research·Shweta KarambelkarValakunja Nagaraja
Apr 11, 2018·Frontiers in Cell and Developmental Biology·Qifan ZhuRamiro Alberio

Methods Mentioned

BETA
TAB-seq
ChIP
PCR
in vitro transcription
ChIP-seq

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