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

TitleNovel Human Embryonic Stem Cell Regulators Identified by Conserved and Distinct CpG Island Methylation State.
Publication TypeJournal Article
Year of Publication2015
AuthorsPells S, Koutsouraki E, Morfopoulou S, Valencia-Cadavid S, Tomlinson SR, Kalathur R, Futschik ME, De Sousa PA
JournalPLoS One
Volume10
Issue7
Paginatione0131102
Date Published2015
ISSN1932-6203
Abstract

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.

DOI10.1371/journal.pone.0131102
Alternate JournalPLoS ONE
PubMed ID26151932
PubMed Central IDPMC4495055
Publication institute
CRM