Integrating 5-Hydroxymethylcytosine into the Epigenomic Landscape of Human Embryonic Stem Cells
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.
Vyšlo v časopise:
Integrating 5-Hydroxymethylcytosine into the Epigenomic Landscape of Human Embryonic Stem Cells. PLoS Genet 7(6): e32767. doi:10.1371/journal.pgen.1002154
Kategorie:
Research Article
prolekare.web.journal.doi_sk:
https://doi.org/10.1371/journal.pgen.1002154
Souhrn
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.
Zdroje
1. JaenischRBirdA 2003 Epigenetic regulation of gene expression: how the genome integrates intrinsic and environmental signals. Nat Genet 33 Suppl 245 254
2. LiEBestorTHJaenischR 1992 Targeted mutation of the DNA methyltransferase gene results in embryonic lethality. Cell 69 915 926
3. OkanoMBellDWHaberDALiE 1999 DNA methyltransferases Dnmt3a and Dnmt3b are essential for de novo methylation and mammalian development. Cell 99 247 257
4. ItoSD'AlessioACTaranovaOVHongKSowersLC 2010 Role of Tet proteins in 5mC to 5hmC conversion, ES-cell self-renewal and inner cell mass specification. Nature 466 1129 1133
5. IyerLMTahilianiMRaoAAravindL 2009 Prediction of novel families of enzymes involved in oxidative and other complex modifications of bases in nucleic acids. Cell Cycle 8 1698 1710
6. KohKPYabuuchiARaoSHuangYCunniffK 2011 Tet1 and tet2 regulate 5-hydroxymethylcytosine production and cell lineage specification in mouse embryonic stem cells. Cell Stem Cell 8 200 213
7. HuangYPastorWAShenYTahilianiMLiuDR 2010 The behaviour of 5-hydroxymethylcytosine in bisulfite sequencing. PLoS ONE 5 e8888 doi:10.1371/journal.pone.0008888
8. JinSGKadamSPfeiferGP 2010 Examination of the specificity of DNA methylation profiling techniques towards 5-methylcytosine and 5-hydroxymethylcytosine. Nucleic Acids Res 38 e125
9. WuHD'AlessioACItoSWangZCuiK 2011 Genome-wide analysis of 5-hydroxymethylcytosine distribution reveals its dual function in transcriptional regulation in mouse embryonic stem cells. Genes and Development April 2011 679-684 679 684
10. WuHD'AlessioACItoSXiaKWangZ 2011 Dual funtions of Tet1 in transcriptional regulation in mouse embryonic stem cells. Nature
11. FiczGBrancoMRSeisenbergerSSantosFKruegerF 2011 Dynamic regulation of 5-hydroxymethylcytosine in mouse ES cells and during differentiation. Nature
12. XuYWuFTanLKongLXiongL 2011 Genome-wide Regulation of 5hmC, 5mC, and Gene Expression by Tet1 Hydroxylase in Mouse Embryonic Stem Cells. Mol Cell
13. WilliamsKChristensenJPedersenMTJohansenJVCloosPA 2011 TET1 and hydroxymethylcytosine in transcription and DNA methylation fidelity. Nature
14. SongCXSzulwachKEFuYDaiQYiC 2011 Selective chemical labeling reveals the genome-wide distribution of 5-hydroxymethylcytosine. Nat Biotechnol 29 68 72
15. HawkinsRDHonGCLeeLKNgoQListerR 2010 Distinct epigenomic landscapes of pluripotent and lineage-committed human cells. Cell Stem Cell 6 479 491
16. ListerRPelizzolaMDowenRHHawkinsRDHonG 2009 Human DNA methylomes at base resolution show widespread epigenomic differences. Nature 462 315 322
17. FerrariRPellegriniMHorwitzGAXieWBerkAJ 2008 Epigenetic reprogramming by adenovirus e1a. Science 321 1086 1088
18. HorwitzGAZhangKMcBrianMAGrunsteinMKurdistaniSK 2008 Adenovirus small e1a alters global patterns of histone modification. Science 321 1084 1085
19. MikkelsenTSKuMJaffeDBIssacBLiebermanE 2007 Genome-wide maps of chromatin state in pluripotent and lineage-committed cells. Nature 448 553 560
20. ChiaNYChanYSFengBLuXOrlovYL 2010 A genome-wide RNAi screen reveals determinants of human embryonic stem cell identity. Nature 468 316 320
21. MaZSwigutTValouevARada-IglesiasAWysockaJ 2011 Sequence-specific regulator Prdm14 safeguards mouse ESCs from entering extraembryonic endoderm fates. Nat Struct Mol Biol 18 120 127
22. TahilianiMKohKPShenYPastorWABandukwalaH 2009 Conversion of 5-methylcytosine to 5-hydroxymethylcytosine in mammalian DNA by MLL partner TET1. Science 324 930 935
23. CoreLJWaterfallJJLisJT 2008 Nascent RNA sequencing reveals widespread pausing and divergent initiation at human promoters. Science 322 1845 1848
24. SeilaACCalabreseJMLevineSSYeoGWRahlPB 2008 Divergent transcription from active promoters. Science 322 1849 1851
25. BangsCDDonlonTA 2005 Metaphase chromosome preparation from cultured peripheral blood cells. Curr Protoc Hum Genet Chapter 4 Unit 4 1
26. ZhangYLiuTMeyerCAEeckhouteJJohnsonDS 2008 Model-based analysis of ChIP-Seq (MACS). Genome Biol 9 R137
27. HonGCHawkinsRDRenB 2009 Predictive chromatin signatures in the mammalian genome. Hum Mol Genet 18 R195 201
28. HonGRenBWangW 2008 ChromaSig: a probabilistic approach to finding common chromatin signatures in the human genome. PLoS Comput Biol 4 e1000201 doi:10.1371/journal.pcbi.1000201
Štítky
Genetika Reprodukčná medicínaČlánok vyšiel v časopise
PLOS Genetics
2011 Číslo 6
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