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CTCF Functions as an Insulator for Somatic Genes and a Structural Regulator for Pluripotent Genes during Reprogramming

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus

PROVIDER: GSE123670 | GEO | 2022/04/05

REPOSITORIES: GEO

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CTCF Functions as an Insulator for Somatic Genes and a Structural Regulator for Pluripotent Genes during Reprogramming [ChIP-seq]

Project description:CCCTC binding factor (CTCF) has been implicated in mediating chromatin insulation and long-distance interactions between enhancer and promoter. In this study, to study the roles of CTCF in somatic cell reprogramming, we performed RNA-seq, Hi-C, ChIP-seq and ATAC-seq at the specific stage of reprogramming. Through bioinformatics analysis, our data indicated that CTCF promotes enhancer-promoter interactions and chromatin accessibility to regulate the expression of key pluripotency genes; meanwhile, it serves as an insulator to suppress the expression of key somatic genes. Smarca5 loss inhibits CTCF-promoted reprogramming by reversing CTCF insulator activity on MEF-specific genes and leading to incorrect nucleosome positioning adjacent to CTCF binding sites. These findings reveal the dual functions of CTCF as both a structural regulator and insulator in conjunction with a key chromatin remodeler to drive cellular reprogramming towards pluripotency.

2022-04-05 | GSE123651 | GEO

CTCF Functions as an Insulator for Somatic Genes and a Structural Regulator for Pluripotent Genes during Reprogramming [ATAC-seq]

2022-04-05 | GSE123667 | GEO

CTCF Functions as an Insulator for Somatic Genes and a Structural Regulator for Pluripotent Genes during Reprogramming [RNA-seq]

2022-04-05 | GSE123641 | GEO

CTCF Functions as an Insulator for Somatic Genes and a Structural Regulator for Pluripotent Genes during Reprogramming [BL-Hi-C]

2022-04-05 | GSE123653 | GEO

CTCF Functions as an Insulator for Somatic Genes and a Structural Regulator for Pluripotent Genes during Reprogramming

Project description:CTCF Functions as an Insulator for Somatic Genes and a Structural Regulator for Pluripotent Genes during Reprogramming

| PRJNA509473 | ENA

CTCF Functions as an Insulator for Somatic Genes and a Structural Regulator for Pluripotent Genes during Reprogramming [ChIP-seq]

Project description:CTCF Functions as an Insulator for Somatic Genes and a Structural Regulator for Pluripotent Genes during Reprogramming [ChIP-seq]

| PRJNA509453 | ENA

CTCF Functions as an Insulator for Somatic Genes and a Structural Regulator for Pluripotent Genes during Reprogramming [ATAC-seq]

Project description:CTCF Functions as an Insulator for Somatic Genes and a Structural Regulator for Pluripotent Genes during Reprogramming [ATAC-seq]

| PRJNA509475 | ENA

CTCF Functions as an Insulator for Somatic Genes and a Structural Regulator for Pluripotent Genes during Reprogramming [RNA-seq]

Project description:CTCF Functions as an Insulator for Somatic Genes and a Structural Regulator for Pluripotent Genes during Reprogramming [RNA-seq]

| PRJNA509452 | ENA

CTCF Functions as an Insulator for Somatic Genes and a Structural Regulator for Pluripotent Genes during Reprogramming [BL-Hi-C]

Project description:CTCF Functions as an Insulator for Somatic Genes and a Structural Regulator for Pluripotent Genes during Reprogramming [BL-Hi-C]

| PRJNA509470 | ENA

Chromosomal aberration arises during somatic reprogramming to pluripotent stem cells.

Project description:BackgroundReprogramming somatic cells to induced pluripotent stem cells (iPSCs) has opened new therapeutic possibilities. However, karyotypic abnormalities detected in iPSCs compromised their utility, especially chromosomal aberrations found at early passages raised serious safety concerns. The mechanism underlying the chromosomal abnormality in early-passage iPSCs is not known.MethodsHuman dermal fibroblasts (HDFs) were stimulated with KMOS (KLF4, cMYC, OCT4 and SOX2) proteins to enhance their proliferative capacity and many vigorous clones were obtained. Clonal reprogramming was carried out by KMOS mRNAs transfection to confirm the 'chromosomal mutagenicity' of reprogramming process. Subculturing was performed to examine karyotypic stability of iPSCs after the re-establishment of stemness. And antioxidant N-acetyl-cysteine (NAC) was added to the culture medium for further confirmming the mutagenicity in the first few days of reprogramming.ResultsChromosomal aberrations were found in a small percentage of newly induced iPS clones by reprogramming transcription factors. Clonal reprogramming ruled out the aberrant chromosomes inherited from rare karyotypically abnormal parental cell subpopulation. More importantly, the antioxidant NAC effectively reduced the occurrence of chromosomal aberrations at the early stage of reprogramming. Once iPS cell lines were established, they restored karyotypic stability in subsequent subculturing.ConclusionsOur results provided the first line of evidence for the 'chromosomal mutagenicity' of reprogramming process.

| S-EPMC7641821 | biostudies-literature

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