Novel Human Embryonic Stem Cell Regulators Identified by Conserved and Distinct CpG Island Methylation State

被引：14

作者：

Pells, Steve ^{[1
,2
]}

Koutsouraki, Eirini ^{[1
]}

Morfopoulou, Sofia ^{[1
]}

Valencia-Cadavid, Sara ^{[1
]}

Tomlinson, Simon R. ^{[1
]}

Kalathur, Ravi ^{[3
]}

Futschik, Matthias E. ^{[3
]}

De Sousa, Paul A. ^{[1
,2
]}

机构：

[1] Univ Edinburgh, Sch Clin Studies, MRC Ctr Regenerat Med, Edinburgh EH16 4SB, Midlothian, Scotland

[2] Univ Edinburgh, Ctr Clin Brain Sci, Edinburgh EH16 4SB, Midlothian, Scotland

[3] Univ Algarve, Ctr Mol & Struct Biomed, P-8005139 Faro, Portugal

来源：

PLOS ONE | 2015年 / 10卷 / 07期

关键词：

DNA METHYLATION; TRANSCRIPTION FACTOR; EPIGENETIC SIGNATURE; GENE-EXPRESSION; SOMATIC-CELLS; HUMAN ES; CULTURE; DIFFERENTIATION; LINES; PLURIPOTENCY;

D O I：

10.1371/journal.pone.0131102

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Human embryonic stem cells (hESCs) undergo epigenetic changes in vitro which may compromise function, so an epigenetic pluripotency "signature" would be invaluable for line validation. We assessed Cytosine-phosphate-Guanine Island (CGI) methylation in hESCs by genomic DNA hybridisation to a CGI array, and saw substantial variation in CGI methylation between lines. Comparison of hESC CGI methylation profiles to corresponding somatic tissue data and hESC mRNA expression profiles identified a conserved hESC-specific methylation pattern associated with expressed genes. Transcriptional repressors and activators were over-represented amongst genes whose associated CGIs were methylated or unmethylated specifically in hESCs, respectively. Knockdown of candidate transcriptional regulators (HMGA1, GLIS2, PFDN5) induced differentiation in hESCs, whereas ectopic expression in fibroblasts modulated iPSC colony formation. Chromatin immunoprecipitation confirmed interaction between the candidates and the core pluripotency transcription factor network. We thus identify novel pluripotency genes on the basis of a conserved and distinct epigenetic configuration in human stem cells.

引用

页数：24

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