Integrating 5-hydroxymethylcytosine into the epigenomic landscape of human embryonic stem cells

Keith E. Szulwach, Xuekun Li, Yujing Li, Chun Xiao Song, Ji Woong Han, Sang Sung Kim, Sandeep Namburi, Karen Hermetz, Julie J. Kim, M. Katharine Rudd, Young Sup Yoon, Bing Ren, Chuan He, Peng Jin

Research output: Contribution to journalArticle

187 Citations (Scopus)

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.

Original languageEnglish
Article numbere1002154
JournalPLoS Genetics
Volume7
Issue number6
DOIs
Publication statusPublished - 2011 Jun 1

Fingerprint

embryonic stem cells
Epigenomics
epigenetics
stem
histones
chromatin
genomics
promoter regions
transcription factors
genome
Embryonic Stem Cells
DNA
Chromatin
Histone Code
5-Methylcytosine
Human Embryonic Stem Cells
5-hydroxymethylcytosine
cells
Histones
Transcription Factors

All Science Journal Classification (ASJC) codes

  • Ecology, Evolution, Behavior and Systematics
  • Molecular Biology
  • Genetics
  • Genetics(clinical)
  • Cancer Research

Cite this

Szulwach, K. E., Li, X., Li, Y., Song, C. X., Han, J. W., Kim, S. S., ... Jin, P. (2011). Integrating 5-hydroxymethylcytosine into the epigenomic landscape of human embryonic stem cells. PLoS Genetics, 7(6), [e1002154]. https://doi.org/10.1371/journal.pgen.1002154
Szulwach, Keith E. ; Li, Xuekun ; Li, Yujing ; Song, Chun Xiao ; Han, Ji Woong ; Kim, Sang Sung ; Namburi, Sandeep ; Hermetz, Karen ; Kim, Julie J. ; Rudd, M. Katharine ; Yoon, Young Sup ; Ren, Bing ; He, Chuan ; Jin, Peng. / Integrating 5-hydroxymethylcytosine into the epigenomic landscape of human embryonic stem cells. In: PLoS Genetics. 2011 ; Vol. 7, No. 6.
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Szulwach, KE, Li, X, Li, Y, Song, CX, Han, JW, Kim, SS, Namburi, S, Hermetz, K, Kim, JJ, Rudd, MK, Yoon, YS, Ren, B, He, C & Jin, P 2011, 'Integrating 5-hydroxymethylcytosine into the epigenomic landscape of human embryonic stem cells', PLoS Genetics, vol. 7, no. 6, e1002154. https://doi.org/10.1371/journal.pgen.1002154

Integrating 5-hydroxymethylcytosine into the epigenomic landscape of human embryonic stem cells. / Szulwach, Keith E.; Li, Xuekun; Li, Yujing; Song, Chun Xiao; Han, Ji Woong; Kim, Sang Sung; Namburi, Sandeep; Hermetz, Karen; Kim, Julie J.; Rudd, M. Katharine; Yoon, Young Sup; Ren, Bing; He, Chuan; Jin, Peng.

In: PLoS Genetics, Vol. 7, No. 6, e1002154, 01.06.2011.

Research output: Contribution to journalArticle

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AU - Han, Ji Woong

AU - Kim, Sang Sung

AU - Namburi, Sandeep

AU - Hermetz, Karen

AU - Kim, Julie J.

AU - Rudd, M. Katharine

AU - Yoon, Young Sup

AU - Ren, Bing

AU - He, Chuan

AU - Jin, Peng

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N2 - 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.

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