Integrating 5-Hydroxymethylcytosine into the Epigenomic Landscape of Human Embryonic Stem Cells
Creators
- 1. Emory University
- 2. University of Chicago
- 3. University of California San Diego
Description
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.
Files
journal.pgen.1002154.pdf
Files
(10.7 MB)
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Additional details
Identifiers
- DOI
- 10.1371/journal.pgen.1002154
- Other
- oai:uchicago.tind.io:10813
Funding
- National Institutes of Health
- NS051630
- National Institutes of Health
- MH076090
- National Institutes of Health
- RC1GM092035
- National Institutes of Health
- GM071440
- Beckman
- Young Investigator Award
- Basil O'Connor
- Scholar Research Award
- Alfred P. Sloan Foundation
- Research Fellow in Neuroscience
- Emory Genetics
- Discovery Fund