Epigenomic Regulation of Human T-Cell Leukemia Virus by Chromatin-Insulator CTCF
Ontology highlight
ABSTRACT:
ORGANISM(S): Human T-cell leukemia virus type I Homo sapiens
PROVIDER: GSE172194 | GEO | 2021/05/08
REPOSITORIES: GEO
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Project description:Chromatin immunopurification with anti-CTCF was used to identify in vivo binding sites for CTCF in approximately 3% of the Drosophila genome using amplicon-based tiling arrays. This includes the Bithorax-complex, a known site of CTCF activity, the Antp-Complex, the Achaete scute-Complex and the Adh region. Reproducible binding identified new CTCF sites in the Adh region and the Bx-C. Keywords: ChIP-chip
2007-06-01 | GSE7351 | GEO
Project description:Role of the bromodomain and extraterminal motif (BET) protein BRD2 in CTCF chromatin occupancy, tested by CRISPR/Cas9-mediated depletion of BRD2 in GATA1-null erythroblasts expressing an inducible GATA1-ER fusion (G1E-ER4). Pharmacologic inhibitors of the BET (bromodomain and extraterminal motif) family of proteins are being explored for the treatment of various diseases, including cancer, yet the individual functions of BET proteins remain unclear. Here we find that BRD2 co-localizes with the architectural/insulator protein CCCTC-binding factor (CTCF) genome-wide. CTCF recruits BRD2 to co-bound sites, whereas BRD2 is dispensable for CTCF occupancy. Genome editing at a CTCF/BRD2 co-occupied site reveals a functional boundary element that upon perturbation results in transcriptional misregulation. Single-molecule RNA FISH reveals that either site-specific CTCF loss or BRD2 depletion increases the correlation in expression of two genes flanking the boundary. Together these findings indicate that BRD2 supports chromatin boundary activity in a CTCF-dependent manner and suggest that pharmacologic BET inhibitors influence gene expression in part by perturbing chromatin domain boundary function.
2017-03-31 | GSE80527 | GEO
Project description:Gain-of-function IDH mutations define major clinical and prognostic classes of gliomas. Mutant IDH protein produces a novel onco-metabolite, 2-hydroxyglutarate (2-HG), that interferes with iron-dependent hydroxylase enzymes, including the TET family of 5'-methylcytosine hydroxylases. TET enzymes are critical for the dynamic regulation of DNA methylation. IDH mutant gliomas thus manifest a CpG island methylator phenotype (G-CIMP), though the functional significance of this altered epigenetic state remains unclear. Here we show that IDH1 mutant gliomas exhibit hyper-methylation at CTCF binding sites, leading to reduced binding of this methylation-sensitive insulator protein. Loss of CTCF binding is associated with a loss of insulation between topological domains and aberrant gene activation. We specifically demonstrate that loss of CTCF at a domain boundary permits a constitutive enhancer to aberrantly interact with the receptor tyrosine kinase gene PDGFRA, a prominent glioma oncogene. Treatment of IDH mutant gliomaspheres with demethylating agent partially restores insulator function and reduces PDGFRA expression. Conversely, CRISPR-mediated disruption of the CTCF binding sequence in IDH wildtype gliomaspheres induces PDGFRA expression and increases proliferation. Our study suggests that IDH mutations promote gliomagenesis by disrupting chromosomal topology and allowing aberrant regulatory interactions that induce oncogene expression. CTCF occupancy characterization and histone H3K27 acetylation profiling in IDH1 mutant and wild-type glioma patient specimens and culture models. ChIP-seq raw data is to be made available through dbGaP (controlled access) due to patient privacy concerns.
2015-12-23 | E-GEOD-70991 | biostudies-arrayexpress
Project description:Aberrant activation of the TAL1 oncogene is associated with up to 60% of T-ALL patients and is involved in CTCF mediated genome organization within the TAL1 locus, suggesting the importance of the CTCF boundary in the molecular pathogenesis of T-ALL. Here, we show that deletion of CTCF binding site (CBS) or alternation of CTCF boundary orientation alters expression of the TAL1 oncogene in a cell context dependent manner. Deletion of the CTCF binding site located at -31 Kb upstream of TAL1 (-31CBS) reduces chromatin accessibility in the +51 enhancer and the TAL1 promoter I, and blocks long-range interaction between the +51 erythroid enhancer and TAL1 promoter 1b that inhibits expression of TAL1 in erythroid cells, but not in T-ALL cells. However, in the TAL1 expressed T-ALL primary patient samples or cell line, the T-ALL prone TAL1 promoter IV specifically interacts with the +19 stem cell enhancer that is located 19 kb downstream of the TAL1 promoter and required for TAL1 transcription in the hematopoietic stem cell (HSC) stage. Inversion of -31CBS orientation, but not deletion of -31CBS, alters chromatin accessibility, enhancer/promoter histone modifications, CTCF-mediated topological associated domain (TAD), and enhancer/promoter interaction in the TAL1 locus leading to inhibition of TAL1 oncogene expression and TAL1-driven T cell leukemogenesis. Thus, our data reveal that the TAL1 +19 stem cell enhancer acts not only as stem cell enhancer, but also as a leukemia specific enhancer to activate the TAL1 oncogene in T-ALL. Manipulation of CTCF defined chromatin boundary can alter TAL1 TAD and oncogenic transcription networks in leukemogenesis.
2020-04-06 | GSE135320 | GEO
Project description:Bovine Leukemia Virus (BLV)-induced tumoral development is a multifactorial phenomenon which remains incompletely understood. Here, we highlight the critical role of the cellular CCCTC-binding factor (CTCF) both in the regulation of BLV transcriptional activities and in the deregulation of the three-dimensional (3D) chromatin architecture surrounding the BLV integration site. We demonstrated the in vivo recruitment of CTCF to three conserved CTCF binding motifs along the BLV provirus. Next, we showed the localization of CTCF to transitions in the histone modifications profile along BLV genome as well as its implication in the repression the 5’Long Terminal Repeat (LTR) promoter activity, thereby contributing to viral latency, while favoring the 3’LTR promoter activity. Finally, we demonstrated that BLV integration deregulated host cellular 3D chromatin organization through the formation of viral/host chromatin loops. Altogether, our results highlight CTCF as a new critical effector of BLV transcriptional regulation and BLV-induced physiopathology.
2022-02-18 | GSE178483 | GEO
Project description:Bovine Leukemia Virus (BLV)-induced tumoral development is a multifactorial phenomenon which remains incompletely understood. Here, we highlight the critical role of the cellular CCCTC-binding factor (CTCF) both in the regulation of BLV transcriptional activities and in the deregulation of the three-dimensional (3D) chromatin architecture surrounding the BLV integration site. We demonstrated the in vivo recruitment of CTCF to three conserved CTCF binding motifs along the BLV provirus. Next, we showed the localization of CTCF to transitions in the histone modifications profile along BLV genome as well as its implication in the repression the 5’Long Terminal Repeat (LTR) promoter activity, thereby contributing to viral latency, while favoring the 3’LTR promoter activity. Finally, we demonstrated that BLV integration deregulated host cellular 3D chromatin organization through the formation of viral/host chromatin loops. Altogether, our results highlight CTCF as a new critical effector of BLV transcriptional regulation and BLV-induced physiopathology.
2022-02-18 | GSE178482 | GEO
Project description:Analysis of Histone H3 Lysine 4 mono-, di- and trimethyl and the boundary protein CTCF in CD4+CD25+CD45RA+ regulatory T-cells and conventional CD4+CD25- T-cells. To investigate regulatory functions or potential new transcription start sites in Treg and Tconv cells, we investigated the associated histone modifications. Mono- and dimethylation of histone 3 lysin 4 (H3K4) were previously shown to mark enhancer regions, whereas H3K4 trimethylation generally associates with transcription start sites. At imprinted loci, binding of the insulator protein CTCF, which restricts or directs enhancer-promoter interactions, is often regulated by DNA-methylation. Therefore we performed ChIP-on-chip experiments (chromatin immunoprecipitation followed by microarray hybridization; samples were amplified with ligation mediated PCR [see label protocol for the procedure] prior to labeling) for mono- di- and trimethylation of histone 3 lysin 4 and of CTCF in expanded Treg and Tconv cells. Keywords: ChIP-on-chip ChIP-on-chip experiments for H3K4 mono-, di- and trimethyl and CTCF in CD4+CD25+CD45RA+ regulatory T-cells and conventional CD4+CD25- T-cells were co-hybridizied with the input. Three biologiacal replicates (rep1-3) were performed for every histone mark, two CTCF (rep1 and rep2).
2010-05-19 | E-GEOD-14234 | biostudies-arrayexpress
Project description:Although the chromatin regulator CTCF is enriched at genes escaping from X-chromosome inactivation (XCI), molecular mechanisms remain elusive. We examined CTCF and epigenetic features at escape genes on the inactive X (Xi) in mouse F1 hybrid cells and tissues. We found that escape genes are located inside topologically insulated domains limited by convergent arrays of CTCF binding sites, suggesting loop formation. Xi-specific deletion of a CTCF right boundary of the escape gene Car5b caused loss of CTCF binding and changes of histone modifications at Car5b and abolished escape, suggesting loss of insulation. This is consistent with Car5b lack of escape in mouse brain showing no CTCF binding at the boundary. Inversion of this boundary had no effect on Car5b escape, suggesting that tandem coiled looping could still function as insulation. To test whether chromatin features of the Xi could affect escape we examined mutants in which the Xi-specific compact structure is disrupted or there is loss of H3K27me3 enrichment. We found that both conditions cause an Xi-specific increase in active marks and gene expression at escape regions, suggesting that the 3D structure and heterochromatic marks of the Xi play a role in modulating escape levels of genes insulated by CTCF.
2023-05-18 | GSE231626 | GEO
Project description:Although the chromatin regulator CTCF is enriched at genes escaping from X-chromosome inactivation (XCI), molecular mechanisms remain elusive. We examined CTCF and epigenetic features at escape genes on the inactive X (Xi) in mouse F1 hybrid cells and tissues. We found that escape genes are located inside topologically insulated domains limited by convergent arrays of CTCF binding sites, suggesting loop formation. Xi-specific deletion of a CTCF right boundary of the escape gene Car5b caused loss of CTCF binding and changes of histone modifications at Car5b and abolished escape, suggesting loss of insulation. This is consistent with Car5b lack of escape in mouse brain showing no CTCF binding at the boundary. Inversion of this boundary had no effect on Car5b escape, suggesting that tandem coiled looping could still function as insulation. To test whether chromatin features of the Xi could affect escape we examined mutants in which the Xi-specific compact structure is disrupted or there is loss of H3K27me3 enrichment. We found that both conditions cause an Xi-specific increase in active marks and gene expression at escape regions, suggesting that the 3D structure and heterochromatic marks of the Xi play a role in modulating escape levels of genes insulated by CTCF.
2025-02-08 | GSE288844 | GEO
Project description:We identified about 3000 CTCF sites in the genome. In addition to binding to CTCF sites we found CP190 to bind to transcriptional start sites of actively transcribed genes where it inversely correlates with nucleosome occupancy. Keywords: ChIP-chip CTCF and CP190 ChIP. 2 biological replicates per experiment. dye-swaps as indicated in sample description.
2010-05-05 | E-GEOD-12749 | biostudies-arrayexpress