TY - JOUR
T1 - 5-Hydroxymethylcytosine is associated with enhancers and gene bodies in human embryonic stem cells
AU - Stroud, Hume
AU - Feng, Suhua
AU - Morey Kinney, Shannon
AU - Pradhan, Sriharsa
AU - Jacobsen, Steven E.
N1 - Funding Information:
HS was supported by a Fred Eiserling and Judith Lengyel Graduate Doctoral Fellowship. SF is a Special Fellow of the Leukemia and Lymphoma Society. Research in the laboratory of SEJ was supported by National Institutes of Health grant GM60398 and by an Innovation Award from the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA. SEJ is an investigator of the Howard Hughes Medical Institute.
PY - 2011/6/20
Y1 - 2011/6/20
N2 - 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.
AB - 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.
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U2 - 10.1186/gb-2011-12-6-r54
DO - 10.1186/gb-2011-12-6-r54
M3 - Article
C2 - 21689397
AN - SCOPUS:79959209733
SN - 1474-7596
VL - 12
JO - Genome biology
JF - Genome biology
IS - 6
M1 - R54
ER -