CTCF deletion alters the pluripotency and DNA methylation profile of human iPSCs (methylation)
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1037541 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:CTCF deletion alters the pluripotency and DNA methylation profile of human iPSCs
| PRJNA1037537 | ENA
Project description:Pluripotent stem cells are characterized by their differentiation potential toward endoderm, mesoderm, and ectoderm. However, it is still largely unclear how these cell-fate decisions are mediated by epigenetic mechanisms. In this study, we explored the relevance of CCCTC-binding factor (CTCF), a zinc finger-containing DNA-binding protein, which mediates long-range chromatin organization, for directed cell-fate determination. We generated human induced pluripotent stem cell (iPSC) lines with deletions in the protein-coding region in exon 3 of CTCF, resulting in overall reduced expression and shorter transcripts. These lines showed a considerable loss of CTCF binding to target sites. The CTCF deletions resulted in slower growth and modest global changes in gene expression, with down-regulation of a subset of pluripotency-associated genes and neuroectodermal genes. CTCF deletion also evoked DNA methylation changes, which were moderately associated with differential gene expression. Notably, CTCF-deletions lead to up-regulation of endo-mesodermal associated marker genes and epigenetic signatures, whereas ectodermal differentiation was defective. These results indicate that CTCF plays an important role in the maintenance of pluripotency and differentiation, especially towards ectodermal lineages.
2023-11-24 | GSE247427 | GEO
Project description:CTCF deletion alters the pluripotency and DNA methylation profile of human iPSCs (ChIP-Seq)
| PRJNA1037539 | ENA
Project description:CTCF deletion alters the pluripotency and DNA methylation profile of human iPSCs (RNA-Seq)
| PRJNA1037540 | ENA
Project description:Pluripotent stem cells are characterized by their differentiation potential toward endoderm, mesoderm, and ectoderm. However, it is still largely unclear how these cell-fate decisions are mediated by epigenetic mechanisms. In this study, we explored the relevance of CCCTC-binding factor (CTCF), a zinc finger-containing DNA-binding protein, which mediates long-range chromatin organization, for directed cell-fate determination. We generated human induced pluripotent stem cell (iPSC) lines with deletions in the protein-coding region in exon 3 of CTCF, resulting in overall reduced expression and shorter transcripts. These lines showed a considerable loss of CTCF binding to target sites. The CTCF deletions resulted in slower growth and modest global changes in gene expression, with down-regulation of a subset of pluripotency-associated genes and neuroectodermal genes. CTCF deletion also evoked DNA methylation changes, which were moderately associated with differential gene expression. Notably, CTCF-deletions lead to up-regulation of endo-mesodermal associated marker genes and epigenetic signatures, whereas ectodermal differentiation was defective. These results indicate that CTCF plays an important role in the maintenance of pluripotency and differentiation, especially towards ectodermal lineages.
2023-11-24 | GSE247426 | GEO
Project description:Pluripotent stem cells are characterized by their differentiation potential toward endoderm, mesoderm, and ectoderm. However, it is still largely unclear how these cell-fate decisions are mediated by epigenetic mechanisms. In this study, we explored the relevance of CCCTC-binding factor (CTCF), a zinc finger-containing DNA-binding protein, which mediates long-range chromatin organization, for directed cell-fate determination. We generated human induced pluripotent stem cell (iPSC) lines with deletions in the protein-coding region in exon 3 of CTCF, resulting in shorter transcripts and overall reduced protein expression. Chromatin immunoprecipitation showed a considerable loss of CTCF binding to target sites. The CTCF deletions resulted in slower growth and modest global changes in gene expression, with downregulation of a subset of pluripotency-associated genes and neuroectodermal genes. CTCF deletion also evoked DNA methylation changes, which were moderately associated with differential gene expression. Notably, CTCF-deletions lead to upregulation of endo-mesodermal associated marker genes and epigenetic signatures, whereas ectodermal differentiation was defective. These results indicate that CTCF plays an important role in the maintenance of pluripotency and differentiation, especially towards ectodermal lineages.
| S-EPMC10720430 | biostudies-literature
Project description:ChIP-Seq analysis of CTCF enrichment in WT hiPSCs and hiPSCs with CTCF deletion
2023-11-24 | GSE247425 | GEO
Project description:This SuperSeries is composed of the SubSeries listed below.
2023-11-24 | GSE247428 | GEO
Project description:A dramatic difference in global DNA methylation between male and female cells characterizes mouse embryonic stem cells (ESCs), unlike somatic cells. We analyzed DNA methylation changes during reprogramming of male and female somatic cells and in resulting induced pluripotent stem cells (iPSCs). At an intermediate reprogramming stage, somatic and pluripotency enhancers are targeted for partial methylation and demethylation. Demethylation within pluripotency enhancers often occurs at ESC binding sites of pluripotency transcription factors. Late in reprogramming, global hypomethylation is induced in a female-specific manner. Genome-wide hypomethylation in female cells affects many genomic landmarks, including enhancers and imprint control regions, and accompanies the reactivation of the inactive X-chromosome. The loss of one of the two X-chromosomes in propagating female iPSCs is associated with genome-wide methylation gain. Collectively, our findings highlight the dynamic regulation of DNA methylation at enhancers during reprogramming and reveal that X-chromosome dosage dictates global DNA methylation levels in iPSCs.
2018-04-19 | GSE111042 | GEO
Project description:Ctcf heterozygous knockout mice are susceptible to neoplasia in a broad range of tissues, including lymphoma, endometrial cancer, and non-small cell lung cancer. Retention of the wild type Ctcf allele in these tumors establishes CTCF as a haploinsufficient tumor suppressor gene. Both human tumors and normal murine tissues with CTCF disruption are characterized by genome-wide differences in DNA methylation relative to CTCF wild type tissues, indicating even modest disruption of CTCF broadly destabilizes DNA methylation in vivo. This cross species functional analysis identifies CTCF as a commonly mutated tumor suppressor gene and establishes a central role for DNA methylation stability in tumor suppression. RRBS sequencing of transgenic Ctcf heterozygous mice and wild-type litter mate whole lung tissue.
2014-07-30 | E-GEOD-48975 | biostudies-arrayexpress