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5-hydroxymethylcytosine represses the activity of enhancers in embryonic stem cells: a new epigenetic signature for gene regulation
- Source :
- BMC Genomics
- Publication Year :
- 2014
-
Abstract
- Background 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. Results 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”. Conclusions Our findings indicate that 5hmC has a repressive role at specific proximal and distal regulatory regions in mESCs, and suggest that 5hmC is a new epigenetic mark for silenced enhancers. Electronic supplementary material The online version of this article (doi:10.1186/1471-2164-15-670) contains supplementary material, which is available to authorized users.
- Subjects :
- eRNA
Enhancer RNAs
Biology
GROseq
Epigenesis, Genetic
Histones
03 medical and health sciences
chemistry.chemical_compound
Cytosine
Mice
0302 clinical medicine
mESC
Genetics
Animals
Cell Lineage
Epigenetics
RNA, Messenger
Enhancer
Transcription factor
Embryonic Stem Cells
030304 developmental biology
Regulation of gene expression
5-Hydroxymethylcytosine
0303 health sciences
Binding Sites
Molecular biology
PolII
Chromatin
Histone
Enhancer Elements, Genetic
chemistry
biology.protein
5-Methylcytosine
5hmC
030217 neurology & neurosurgery
Biotechnology
Transcription Factors
Research Article
Subjects
Details
- ISSN :
- 14712164
- Volume :
- 15
- Database :
- OpenAIRE
- Journal :
- BMC genomics
- Accession number :
- edsair.doi.dedup.....c10c52cc5f93f822506bbb4b7871f0ff