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.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4495055 | PMC |
| http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0131102 | PLOS |
Publication Analysis
Top Keywords
Similar Publications
LncRNA Recognition-Associated CpG Island Detection and Methylation Analysis.
Methods Mol Biol
December 2024
College of computer science, Sichuan University, Chengdu, China.
CpG islands (CGIs) are rare, interspersed DNA sequences, which possess a significant deviation from background genomic distribution by exhibiting patterns of GC-rich and CpG-rich sequence, the density of which provides a good classification feature for long noncoding RNA (lncRNA) promoters. By reviewing previous CpG-related studies, we consider that the transcription regulation of about half of the human genes, mostly housekeeping (HK) genes, involves CGIs, their methylation states, CpG spacing, and other chromosomal parameters. However, the precise CGI definition and positioning of CGIs within gene structures, as well as specific CGI-associated regulatory mechanisms, all remain to be elucidated at individual gene and gene family levels, together with consideration of species and lineage specificity.
View Article and Find Full Text PDFDNA methylation profiling of CpG islands in trigeminal ganglion of rats with orofacial pain induced by experimental tooth movement.
BMC Oral Health
December 2024
Department of Pediatric Dentistry, Stomatology Hospital, School of Stomatology, Zhejiang University School of Medicine, Zhejiang Provincial Clinical Research Center for Oral Diseases, Key Laboratory of Oral Biomedical Research of Zhejiang Province, Cancer Center of Zhejiang University, Engineering Research Center of Oral Biomaterials and Devices of Zhejiang Province, Hangzhou, 310000, China.
Background: Tooth movement induced orofacial pain is the most cited negative effect during orthodontic treatment, while treatment options without side effects are limited. The differential expression of pain-related genes due to DNA methylation and demethylation is instrumental in pain. The purpose of the study was to evaluate the DNA methylation profiling of CpG islands (CGI) and CGI shores in promoter regions in trigeminal ganglions (TG) of tooth movement induced orofacial pain rats, thus to further insight the DNA methylation regulation in orofacial pain.
View Article and Find Full Text PDFKDM5C is a sex-biased brake against germline gene expression programs in somatic lineages.
bioRxiv
November 2024
Department of Human Genetics, Michigan Medicine, University of Michigan Medical School, Ann Arbor, MI, 48109, USA.
The division of labor among cellular lineages is a pivotal step in the evolution of multicellularity. In mammals, the soma-germline boundary is formed during early embryogenesis, when genes that drive germline identity are repressed in somatic lineages through DNA and histone modifications at promoter CpG islands (CGIs). Somatic misexpression of germline genes is a signature of cancer and observed in select neurodevelopmental disorders.
View Article and Find Full Text PDFUnraveling the DNA methylation landscape in dog blood across breeds.
BMC Genomics
November 2024
Graduate School of Veterinary Medicine, Veterinary Teaching Hospital, Hokkaido University, Sapporo, Japan.
Background: DNA methylation is a covalent bond modification that is observed mainly at cytosine bases in the context of CG pairs. DNA methylation patterns reflect the status of individual tissues, such as cell composition, age, and the local environment, in mammals. Genetic factors also impact DNA methylation, and the genetic diversity among various dog breeds provides a valuable platform for exploring this topic.
View Article and Find Full Text PDFKDM2A and KDM2B protect a subset of CpG islands from DNA methylation.
J Genet Genomics
November 2024
State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, China. Electronic address:
In the mammalian genome, most CpGs are methylated. However, CpGs within the CpG islands (CGIs) are largely unmethylated, which are important for gene expression regulation. The mechanism underlying the low methylation levels at CGIs remains largely elusive.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!