A genome-wide map of CTCF multivalency redefines the CTCF code
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ABSTRACT:
PROVIDER: PRJNA148151 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR372712.fastq.gz | Fastqsanger.gz | |||
| SRR372713.fastq.gz | Fastqsanger.gz | |||
| SRR836456.fastq.gz | Fastqsanger.gz | |||
| SRR836457.fastq.gz | Fastqsanger.gz | |||
| SRR836458.fastq.gz | Fastqsanger.gz |
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Project description:The “CTCF code” hypothesis posits that CTCF pleotropic functions are driven by recognition of diverse DNA sequences through combinatorial use of its 11 zinc fingers (ZFs). This model however is supported by in vitro binding studies of a limited number of sequences. To directly test CTCF multivalency in vivo we here define ZF binding requirements at ~50,000 genomic sites in primary lymphocytes. We find that CTCF reads sequence diversity through ZF clustering. ZFs4-7 anchor CTCF to ~80% of targets containing the 20bp core motif. Non-conserved flanking sequences are recognized by ZFs1-2 and ZFs8- 11 clusters, which also stabilize CTCF broadly. Alternatively, CTCF employ ZFs9-11 to associate with a second phylogenetically-conserved upstream motif at ~15% of its sites. Individually, ZFs increase overall binding affinity and chromatin residence time. Unexpectedly, we also uncover a conserved downstream DNA motif that destabilizes CTCF occupancy. CTCF thus associates with a wide array of DNA modules via combinatorial clustering of its 11 ZFs.
2011-11-19 | GSE33819 | GEO
Project description:The "CTCF code" hypothesis posits that CTCF pleiotropic functions are driven by recognition of diverse sequences through combinatorial use of its 11 zinc fingers (ZFs). This model, however, is supported by in vitro binding studies of a limited number of sequences. To study CTCF multivalency in vivo, we define ZF binding requirements at ∼50,000 genomic sites in primary lymphocytes. We find that CTCF reads sequence diversity through ZF clustering. ZFs 4-7 anchor CTCF to ∼80% of targets containing the core motif. Nonconserved flanking sequences are recognized by ZFs 1-2 and ZFs 8-11 clusters, which also stabilize CTCF broadly. Alternatively, ZFs 9-11 associate with a second phylogenetically conserved upstream motif at ∼15% of its sites. Individually, ZFs increase overall binding and chromatin residence time. Unexpectedly, we also uncovered a conserved downstream DNA motif that destabilizes CTCF occupancy. Thus, CTCF associates with a wide array of DNA modules via combinatorial clustering of its 11 ZFs.
| S-EPMC3770538 | biostudies-literature
Project description:The transcription factor CTCF appears indispensable in defining topologically associated domain boundaries and maintaining chromatin loop structures within these domains, supported by numerous functional studies. However, acute depletion of CTCF globally reduces chromatin interactions but does not significantly alter transcription. Here we systematically integrated multi-omics data including ATAC-seq, RNA-seq, WGBS, Hi-C, Cut&Run, CRISPR-Cas9 survival dropout screening, time-solved deep proteomic and phosphoproteomic analyses in cells carrying auxin-induced degron at endogenous CTCF locus. Acute CTCF protein degradation markedly rewired genome-wide chromatin accessibility. Increased accessible chromatin regions were largely located adjacent to CTCF-binding sites at promoter regions and insulator sites and were associated with enhanced transcription of nearby genes. In addition, we used CTCF-associated multi-omics data to establish a combinatorial data analysis pipeline to discover CTCF co-regulatory partners in regulating downstream gene expression. We successfully identified 40 candidates, including multiple established partners (i.e., MYC) supported by all layers of evidence. Interestingly, many CTCF co-regulators (e.g., YY1, ZBTB7A) that have evident alterations of respective downstream gene expression do not show changes at their expression levels across the multi-omics measurements upon acute CTCF loss, highlighting the strength of our system to discover hidden co-regulatory partners associated with CTCF-mediated transcription. This study highlights CTCF loss rewires genome-wide chromatin accessibility, which plays a critical role in transcriptional regulation
2021-07-04 | PXD026484 | Pride
Project description:Insulators are DNA elements, which prevent inappropriate interactions between the neighboring regions of the genome. They can be functionally classified as either enhancer blockers or domain barriers. CTCF (CCCTC binding factor) is the only known major insulator binding protein in the vertebrates and has been shown to bind many enhancer-blocking elements. However, it is not clear whether it plays a role in chromatin domain barriers between active and repressive domains. Here, we used ChIP-Seq to map the genome-wide binding sites of CTCF in three cell types and identified significant binding of CTCF to the boundaries of repressive chromatin domains marked by H3K27me3. Although we find an extensive overlapping of CTCF binding sites across the three cell types, its association with the domain boundaries is cell type-specific. We further show that the nucleosomes flanking CTCF binding sites are well positioned and associated with histone H2AK5 acetylation (H2AK5ac). Interestingly, we found a complementary pattern between the repressive H3K27me3 and the active H2AK5ac regions, which are separated by CTCF. Our findings indicate that CTCF may play important roles in the barrier activity of insulators and provide a resource for further investigation of the CTCF function in organizing chromatin in the human genome. Examination of the role of CTCF in chromatin domain barrier function In addition to the ChIP-seq analysis, two replicates of HeLa expression data were studied.
2008-10-20 | E-GEOD-12889 | biostudies-arrayexpress
Project description:Genome-wide maps of CTCF in glioblastoma
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Project description:A chromatin code for alternative splicing involving an association between CTCF and HP1α proteins
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Project description:Here we have used CTCF ChIP-seq in glioblastoma to understand CTCF elements in the context of chromatin topology genome-wide.
2019-11-25 | GSE139416 | GEO
Project description:A pairwise cytokine code explains the organism-wide response to sepsis
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Project description:CCCTC-binding factor (CTCF) is an architectural protein with context dependent functional outcomes. Although CTCF is conserved throughout Metazoan evolution, its functions have been only evaluated in a limited number of species. Here, we present the first analysis of CTCF binding in the zebrafish genome via chromatin immunoprecipitation followed by sequencing (ChIP-seq). To avoid the need of custom antibodies, we generated a transgenic line with an HA-tagged version of CTCF that enabled the identification of 37,625 CTCF peaks in 24 hours post-fertilization (hpf) embryos. We determined that CTCF peaks generally overlap with histone marks associated to enhancers and active promoters, and identified repeats that are enriched on CTCF binding sites. In addition, we show extended sites of CTCF binding as previously shown in mammals and lamprey, supporting the hypothesis of a CTCF “code” in vertebrates. Our results indicate a positive association between the abundance of CTCF at promoters and gene expression that could be explained by high DNA accessibility. Finally, analysis of chromosome conformation capture data confirms that histone marks associated with active chromatin are enriched at boundaries of topologically associating domains (TADs), but no general enrichment of CTCF peaks nor motifs is observed at these regions. Our zebrafish line and data generated will be important for future studies of genome organization aiming to characterize the roles of CTCF in non-mammalian vertebrates.
2020-03-30 | GSE133437 | GEO
Project description:Accumulated data suggest that transcription factor CTCF is indispensable to define topologically associated domain (TAD) boundaries and to maintain intra-TAD chromatin loop structures. However, upon genome-wide acute depletion of CTCF, the discrepancy between global reduction of chromatin interactions and minimal alteration of transcription has been evidently observed. To understand CTCF’s direct role in chromatin accessibility and global transcriptional regulation, we have systematically integrated data collected from ATAC-seq, RNA-seq, whole genome bisulfite-seq, Cut&Run and HiC in a previously established CTCF-miniAID knock-in cell lines. Acute degradation of CTCF markedly rewires genome-wide chromatin accessibility but not DNA methylation. Differentially altered ATAC-seq peaks are highly associated with adjacent CTCF binding sites, supporting the direct link between CTCF occupancy and its surrounding chromatin accessibility. Increased ATAC-seq peaks upon CTCF loss are notably associated with enhanced transcription at promoter regions and insulator sites, while decreased ATAC-seq peaks are significantly enriched at DNA loops. Furthermore, using CTCF associated multi-Omics data we have established a combinatorial data analysis pipeline to discover novel CTCF mediated insulators in the genome, by which we have successfully identified 67 novel insulators at non-coding regions distal to promoters. Functional CRISPR interference (CRISPRi) unconstrained the repressive transcriptional regulation of target genes. In sum, using CTCF acute depletion cell model and multi-Omics analysis, we concluded that CTCF loss rewires genome-wide chromatin accessibility, which plays a critical role for transcriptional regulation.
2021-08-26 | GSE153237 | GEO