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Constitutively bound CTCF sites maintain 3D chromatin architecture and long-range epigenetically regulated domains

ABSTRACT: Constitutively bound CTCF sites maintain 3D chromatin architecture and long-range epigenetically regulated domains

PROVIDER: PRJNA517606 | ENA |

REPOSITORIES: ENA

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Constitutively bound CTCF sites maintain 3D chromatin architecture and long-range epigenetically regulated domains.

Project description:The architectural protein CTCF is a mediator of chromatin conformation, but how CTCF binding to DNA is orchestrated to maintain long-range gene expression is poorly understood. Here we perform RNAi knockdown to reduce CTCF levels and reveal a shared subset of CTCF-bound sites are robustly resistant to protein depletion. The 'persistent' CTCF sites are enriched at domain boundaries and chromatin loops constitutive to all cell types. CRISPR-Cas9 deletion of 2 persistent CTCF sites at the boundary between a long-range epigenetically active (LREA) and silenced (LRES) region, within the Kallikrein (KLK) locus, results in concordant activation of all 8 KLK genes within the LRES region. CTCF genome-wide depletion results in alteration in Topologically Associating Domain (TAD) structure, including the merging of TADs, whereas TAD boundaries are not altered where persistent sites are maintained. We propose that the subset of essential CTCF sites are involved in cell-type constitutive, higher order chromatin architecture.

| S-EPMC6946690 | biostudies-literature

Constitutively bound CTCF sites maintain 3D chromatin architecture and long-range epigenetically regulated domains

Project description:This SuperSeries is composed of the SubSeries listed below.

2019-11-18 | GSE125641 | GEO

KDM4C epigenetically regulates and forms a feed-forward loop with ALDH1A3 to maintain gastric cancer stemness

Project description:Gastric cancer (GC) stem cells (GCSCs) are characterized as high level of ALDH activity, however, the mechanisms of maintenance of high ALDH activity and stemness in GCSCs are largely unknown. Here, we report that KDM4C, a H3K9me2/3-demethylase, epigenetically regulates ALDH1A3 by histone demethylation and forms a feed-forward loop with ALDH1A3 to supports GS stemness. Ectopic expression of both KDM4C and ALDH1A3 promotes the properties of GCSCs, including spherogenecity, self-renewal, CD44 expression and ALDH activity; knockdown of anyone abolished the effect of each other. KDM4C directly binds to the promoter of ALDH1A3, leads to histone demethylation, thereby promoting ALDH1A3 transcription. Upregulated ALDH1A3 in turn transcriptionally upregulates KDM4C. Simultaneous inhibition of KDM4C and ALDH1A3 synergistically sensitizes GC sphere-derived cells to traditional chemotherapeutic drugs. The finding that upregulated ALDH1A3 promotes its own transcription via KDM4C-mediated epigenetic modification represents an important feed-forward mechanism for GCSCs to maintain stemness and promote tumourigenesis and our work thus suggests a novel therapeutic strategy for eradicating human GCSCs. To investigate the mechanisms underlying KDM4C promoting CG stemness, we identified the differentially expressed proteins (DEPs) between KDM4C-overexpressing and control AGS cells by iTRAQ-based quantitative proteomic analysis.

2022-02-16 | PXD023455 | Pride

Constitutively Active Foxo3 in Oocytes Preserves Ovarian Reserve in Mice

Project description:During female reproductive life, the reserve of ovarian follicles is reduced by maturation and atresia until menopause ensues. Foxo3 is required to maintain the ovarian reserve in mice. We asked if overexpression of a constitutively active FOXO3 protein can increase long-lasting ovarian reproductive capacity in mice.

2013-06-08 | GSE45389 | GEO

Constitutively Active Foxo3 in Oocytes Preserves Ovarian Reserve in Mice

2013-06-08 | E-GEOD-45389 | biostudies-arrayexpress

SCML2 establishes germline-specific bivalent domains.

Project description:Bivalent domains marked with repressive H3K27me3 and activating H3K4me2/3 are a molecular signature of totipotency in stem cells and development. While bivalent domains are retained throughout the germline to recover totipotency in the next generation, the mechanisms establishing bivalent domains remains unknown. Here we demonstrate that a germline-specific Polycomb protein, SCML2, binds to chromatin containing hypomethylated DNA to induce H3K27me3, thereby initiating the establishment of germline-specific bivalent domains in mice. SCML2 regulates two distinct classes of autosomal bivalent domains, the first are maintained constitutively through spermatogenesis (Class I), and the second are specifically established during meiosis (Class II). In postmeiotic spermatids, the loss of H3K27me3 leads to an increase of H3K4me2/3 on bivalent domains and disorganization of pericentromic heterochromatin. We propose that SCML2 regulates dynamic bivalent domains in the germline as a molecular imprint to recover totipotency after fertilization.

2018-04-12 | GSE89502 | GEO

Constitutively Active YAP/TAZ Target Genes

Project description:Constitutively Active YAP/TAZ Target Genes

| PRJNA489431 | ENA

The FUN30 Chromatin Remodeler Fft3 Protects Centromeric and Subtelomeric Domains from Euchromatin Formation

Project description:The chromosomes of eukaryotes are organized into structurally and functionally discrete domains. This implies the presence of insulator elements that separate adjacent domains, allowing them to maintain different chromatin structures. We show that the Fun30 chromatin remodeler, Fft3, is essential for maintaining a proper chromatin structure at centromeres and subtelomeres. Fft3 is localized to insulator elements and inhibits euchromatin assembly in silent chromatin domains. In its absence, euchromatic histone modifications and histone variants invade centromeres and subtelomeres, causing a mis-regulation of gene expression and severe chromosome segregation defects. Our data strongly suggest that Fft3 controls the identity of chromatin domains by protecting these regions from euchromatin assembly.

2011-04-02 | E-MEXP-3044 | biostudies-arrayexpress

Expression analysis of Reh cells after transfection with constitutively active variants of IRF5 (IRF5-4D) and/or constitutively active IKKβ(EE)

Project description:Genome-wide gene expression analysis of Reh cells following transfection with constitutively active IRF5-4D, constitutively active IKKβ(EE), or both in combination.

2014-09-24 | GSE51717 | GEO

Expression analysis of Reh cells after transfection with constitutively active variants of IRF5 (IRF5-4D) and/or constitutively active IKKÎ²(EE)

Project description:Genome-wide gene expression analysis of Reh cells following transfection with constitutively active IRF5-4D, constitutively active IKKÎ²(EE), or both in combination. Affymetrix U133 Plus 2.0 oligonucleotide arrays were hybridized to determine the gene expression profile of acute lymphoblastic leukemia-derived Reh cells following transfection with i) control constructs, ii), a constitutively active variant of IRF5 (IRF5-4D), iii) a constitutively active variant of the IkB kinase Î² (IKKÎ²(EE)), or iv) IRF5-4D in combination with IKKÎ²(EE). All hybridizations were done in biological duplicates.

2014-09-24 | E-GEOD-51717 | biostudies-arrayexpress

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