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

Journal Article

TítuloNovel Human Embryonic Stem Cell Regulators Identified by Conserved and Distinct CpG Island Methylation State.
Publication TypeJournal Article
AuthorsPells, S, Koutsouraki, E, Morfopoulou, S, Valencia-Cadavid, S, Tomlinson, SR, Kalathur, R, Futschik, ME, De Sousa, PA
Year of Publication2015
JournalPLoS One
Date Published2015
Palavras-chaveCell Differentiation, Cell Line, Cells, Cultured, CpG Islands, DNA Methylation, Epigenesis, Genetic, Epigenomics, Female, Fibroblasts, Gene Expression Profiling, Gene Regulatory Networks, HMGA1a Protein, Human Embryonic Stem Cells, Humans, Induced Pluripotent Stem Cells, Kruppel-Like Transcription Factors, Male, Protein Binding, Repressor Proteins, RNA Interference

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.


Alternate JournalPLoS ONE
PubMed ID26151932
PubMed Central IDPMC4495055
Grant ListMRC_G0300484 / / Medical Research Council / United Kingdom
CCMAR Authors