Similar Datasets
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:CTCF-mediated insulation and chromatin environment modulate Car5b escape from X inactivation
| PRJNA1219595 | ENA
Project description:CTCF-mediated insulation and chromatin environment modulate Car5b escape from X inactivation I
| PRJNA967025 | ENA
Project description:CTCF-mediated insulation and chromatin environment modulate Car5b escape from X inactivation II
| PRJNA1219604 | ENA
Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series
2015-02-20 | E-GEOD-59779 | biostudies-arrayexpress
Project description:Angiogenesis is meticulously controlled by a fine balance between positive and negative regulatory activities. Vascular endothelial growth factor (VEGF) is a predominant angiogenic factor and its dosage is precisely regulated during normal vascular formation. In cancer, VEGF is commonly overproduced, resulting in abnormal neovascularization. VEGF is induced in response to various stimuli including hypoxia; however, very little is known about the mechanisms that confine its induction to ensure proper angiogenesis. Chromatin insulation is a key transcription mechanism that prevents promiscuous gene activation by interfering with the action of enhancers. Here we show that the chromatin insulator-binding factor CTCF binds to the proximal promoter of VEGF. Consistent with the enhancer-blocking mode of chromatin insulators, CTCF has little effect on basal expression of VEGF but specifically affects its activation by enhancers. CTCF knockdown cells are sensitized for induction of VEGF and exhibit elevated proangiogenic potential. Cancer-derived CTCF missense mutants are mostly defective in blocking enhancers at the VEGF locus. Moreover, during mouse retinal development, depletion of CTCF causes excess angiogenesis. Therefore, CTCF-mediated chromatin insulation acts as a crucial safeguard against hyperactivation of angiogenesis.
| S-EPMC3174592 | biostudies-literature
Project description:MotivationThe three dimensional organization of chromosomes within the cell nucleus is highly regulated. It is known that CCCTC-binding factor (CTCF) is an important architectural protein to mediate long-range chromatin loops. Recent studies have shown that the majority of CTCF binding motif pairs at chromatin loop anchor regions are in convergent orientation. However, it remains unknown whether the genomic context at the sequence level can determine if a convergent CTCF motif pair is able to form a chromatin loop.ResultsIn this article, we directly ask whether and what sequence-based features (other than the motif itself) may be important to establish CTCF-mediated chromatin loops. We found that motif conservation measured by 'branch-of-origin' that accounts for motif turn-over in evolution is an important feature. We developed a new machine learning algorithm called CTCF-MP based on word2vec to demonstrate that sequence-based features alone have the capability to predict if a pair of convergent CTCF motifs would form a loop. Together with functional genomic signals from CTCF ChIP-seq and DNase-seq, CTCF-MP is able to make highly accurate predictions on whether a convergent CTCF motif pair would form a loop in a single cell type and also across different cell types. Our work represents an important step further to understand the sequence determinants that may guide the formation of complex chromatin architectures.Availability and implementationThe source code of CTCF-MP can be accessed at: https://github.com/ma-compbio/CTCF-MP.Supplementary informationSupplementary data are available at Bioinformatics online.
| S-EPMC6022626 | biostudies-literature
Project description:Insulators play a critical role in spatiotemporal gene regulation in animals. The evolutionarily conserved CCCTC-binding factor (CTCF) is required for insulator function in mammals, but not all of its binding sites act as insulators. Here we explore the sequence requirements of CTCF-mediated transcriptional insulation using a sensitive insulator reporter in mouse embryonic stem cells. We find that insulation potency depends on the number of CTCF-binding sites in tandem. Furthermore, CTCF-mediated insulation is dependent on upstream flanking sequences at its binding sites. CTCF-binding sites at topologically associating domain boundaries are more likely to function as insulators than those outside topologically associating domain boundaries, independently of binding strength. We demonstrate that insulators form local chromatin domain boundaries and weaken enhancer-promoter contacts. Taken together, our results provide genetic, molecular and structural evidence connecting chromatin topology to the action of insulators in the mammalian genome.
| S-EPMC8853952 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below.
2020-07-06 | GSE153403 | GEO