title: 5-Hydroxymethylcytosine is associated with enhancers and gene bodies in human embryonic stem cells.
abstract: BACKGROUND
  5-Hydroxymethylcytosine (5hmC) was recently found to be abundantly present in certain cell types, including embryonic stem cells. There is growing evidence that TET proteins, which convert 5-methylcytosine (5mC) to 5hmC, play important biological roles. To further understand the function of 5hmC, an analysis of the genome-wide localization of this mark is required.
  
  
  RESULTS
  Here, we have generated a genome-wide map of 5hmC in human embryonic stem cells by hmeDIP-seq, in which hydroxymethyl-DNA immunoprecipitation is followed by massively parallel sequencing. We found that 5hmC is enriched in enhancers as well as in gene bodies, suggesting a potential role for 5hmC in gene regulation. Consistent with localization of 5hmC at enhancers, 5hmC was significantly enriched in histone modifications associated with enhancers, such as H3K4me1 and H3K27ac. 5hmC was also enriched in other protein-DNA interaction sites, such as OCT4 and NANOG binding sites. Furthermore, we found that 5hmC regions tend to have an excess of G over C on one strand of DNA.
  
  
  CONCLUSIONS
  Our findings suggest that 5hmC may be targeted to certain genomic regions based both on gene expression and sequence composition.
authors.affiliation: Department of Molecular, Cell and Developmental Biology, University of California-Los Angeles, CA 90095, USA.
authors.forename: Hume
authors.initials: H
authors.lastname: Stroud
authors.forename: Suhua
authors.initials: S
authors.lastname: Feng
authors.forename: Shannon
authors.initials: S
authors.lastname: Morey Kinney
authors.forename: Sriharsa
authors.initials: S
authors.lastname: Pradhan
authors.forename: Steven E
authors.initials: SE
authors.lastname: Jacobsen
mesh_terms: D044503:5-Methylcytosine / Q000031:analogs & derivatives; D001482:Base Composition; D001665:Binding Sites / Q000235:genetics; D003596:Cytosine / Q000031:analogs & derivatives* / Q000378:metabolism; D053595:Embryonic Stem Cells / Q000378:metabolism*; D004742:Enhancer Elements, Genetic; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D014157:Transcription Factors; C011865:5-hydroxymethylcytosine; D044503:5-Methylcytosine; D003596:Cytosine