title: Integrating 5-hydroxymethylcytosine into the epigenomic landscape of human embryonic stem cells.
abstract: Covalent modification of DNA distinguishes cellular identities and is crucial for regulating the pluripotency and differentiation of embryonic stem (ES) cells. The recent demonstration that 5-methylcytosine (5-mC) may be further modified to 5-hydroxymethylcytosine (5-hmC) in ES cells has revealed a novel regulatory paradigm to modulate the epigenetic landscape of pluripotency. To understand the role of 5-hmC in the epigenomic landscape of pluripotent cells, here we profile the genome-wide 5-hmC distribution and correlate it with the genomic profiles of 11 diverse histone modifications and six transcription factors in human ES cells. By integrating genomic 5-hmC signals with maps of histone enrichment, we link particular pluripotency-associated chromatin contexts with 5-hmC. Intriguingly, through additional correlations with defined chromatin signatures at promoter and enhancer subtypes, we show distinct enrichment of 5-hmC at enhancers marked with H3K4me1 and H3K27ac. These results suggest potential role(s) for 5-hmC in the regulation of specific promoters and enhancers. In addition, our results provide a detailed epigenomic map of 5-hmC from which to pursue future functional studies on the diverse regulatory roles associated with 5-hmC.
authors: Department of Human Genetics, Emory University School of Medicine, Atlanta, Georgia, United States of America.
authors: Keith E
authors: KE
authors: Szulwach
authors: Xuekun
authors: X
authors: Li
authors: Yujing
authors: Y
authors: Li
authors: Chun-Xiao
authors: CX
authors: Song
authors: Ji Woong
authors: JW
authors: Han
authors: SangSung
authors: S
authors: Kim
authors: Sandeep
authors: S
authors: Namburi
authors: Karen
authors: K
authors: Hermetz
authors: Julie J
authors: JJ
authors: Kim
authors: M Katharine
authors: MK
authors: Rudd
authors: Young-Sup
authors: YS
authors: Yoon
authors: Bing
authors: B
authors: Ren
authors: Chuan
authors: C
authors: He
authors: Peng
authors: P
authors: Jin
mesh_terms: D044503:5-Methylcytosine / Q000378:metabolism / Q000031:analogs & derivatives; D001665:Binding Sites; D002460:Cell Line; D002874:Chromosome Mapping; D003596:Cytosine / Q000031:analogs & derivatives* / Q000378:metabolism; D019175:DNA Methylation; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000378:metabolism; D057890:Epigenomics; D005786:Gene Expression Regulation; D015723:Gene Library; D015894:Genome, Human; D006570:Heterochromatin / Q000737:chemistry; D006657:Histones / Q000378:metabolism; D006801:Humans; D015151:Immunoblotting; D008677:Metaphase; D011401:Promoter Regions, Genetic; D016415:Sequence Alignment; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D006570:Heterochromatin; D006657:Histones; D014157:Transcription Factors; C011865:5-hydroxymethylcytosine; D044503:5-Methylcytosine; D003596:Cytosine