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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:Topological domains are key architectural building blocks of chromosomes in complex genomes. Their functional importance and evolutionary dynamics are however not well defined. Here we performed comparative Hi-C in liver cells from four mammalian species, and characterized the conservation and divergence of chromosomal contact insulation and the resulting domain architectures within distantly related genomes. We show that the modular organization of chromosomes is robustly conserved in syntenic regions. This overall conservation is compatible with conservation of the binding landscape of the insulator protein CTCF. Specifically, conserved CTCF sites are co-localized with cohesin, enriched at strong topological domain borders and bind to DNA motifs with orientations that define the directionality of CTCF’s long-range interactions. Interestingly, CTCF binding sites which are divergent between species are strongly correlated with divergence of internal domain structure. This divergence is likely driven by local CTCF binding sequence changes, demonstrating how genome evolution can be linked directly with a continuous flux of local chromosome conformation changes. Conversely, we provide evidence that large-scale domains are harder to break and that they are reorganized during genome evolution as intact modules. Hi-C and 4C-seq experiments were conducted in primary liver cells obtained from mouse, rabbit, macaque and dog
2015-02-26 | E-GEOD-65126 | biostudies-arrayexpress
Project description:The homeotic genes (Hox genes) encode transcription factors (HOX-TFs) that are key regulators of animal development. Single and compound deletion of Hox genes in mice revealed that they act in a partially redundant manner to pattern the vertebrate limb. Biochemical screens probing the sequence specificity of the DNA-binding domains showed that HOX-TFs recognize largely similar DNA sequences, but also emphasized the important role of co-factors in HOX DNA-binding. However, due to their high sequence homology and overlapping expression patterns, little is known about the genome-wide binding of these transcription factors Here, we set out to systematically compare the effects of the nine limb-bud expressed HOX-TFs on cell differentiation and gene regulation, and compare their genome-wide binding characteristics. We find that HOX-TFs induce distinct regulatory programs in transduced cells. Through genome-wide DNA binding profiling we find that the posterior HOX-TFs can be separated into two groups with distinct binding motifs and association with co-factors. Through this unexpected grouping, we characterize the CCCTC-binding factor (CTCF) as a novel co-factor of HOX-TFs and show that one, but not the other group of HOX-TFs binds to thousands of CTCF-occupied sites in the chicken genome.
2016-12-31 | GSE86088 | GEO
Project description:CTCF is a master regulator that plays a role in genome architecture and gene expression. A key aspect of CTCF’s mechanism involves bringing together distant genetic elements for intra- and inter-chromosomal interactions. Evidence from epigenetic processes, such as X-chromosome inactivation (XCI), suggests that CTCF may carry out its functions through interacting RNAs. Using genome-wide approaches to investigate the relationship between CTCF’s RNA interactome and its epigenomic landscape, here we report that CTCF interacts with thousands of transcripts in mouse embryonic stem cells (mESC), many in close proximity to CTCF’s genomic binding sites. Biochemical analysis demonstrates that CTCF is a high-affinity RNA binding protein that contacts RNA directly and specifically. In the XCI model, CTCF binds the active and inactive X-chromosomes allele-specifically. At the X-inactivation center, Tsix RNA binds CTCF and targets CTCF to a region associated with X-chromosome pairing. Our work implicates CTCF-RNA interactions in long-range chromosomal interactions in trans and adds a new layer of complexity to CTCF regulation. The genome-wide datasets reported here will provide a useful resource for further study of CTCF-mediated epigenomic regulation. CTCF RNA interactome was identified by UV-crosslinking and immunoprecipitation followed by high-throughput sequencing (CLIP-seq), and was compared to CTCF's epigenomic landscape as obtained by chromatin immunoprecipitation (ChIP-seq).
2015-01-09 | E-GEOD-58242 | biostudies-arrayexpress
Project description:The roles of topoisomerases in somatic mutagenesis in cancer are poorly understood and their DNA-binding landscape remains largely unmapped. Here we generated genome-wide DNA-binding maps of TOP2B, CTCF, and RAD21 in human hepatocellular carcinoma samples.
2024-02-01 | E-MTAB-13301 | biostudies-arrayexpress
Project description:CTCF binding evolution in mammals
| PRJEB2329 | ENA
Project description:The homeotic genes (Hox genes) encode transcription factors (HOX-TFs) that are key regulators of animal development. Single and compound deletion of Hox genes in mice revealed that they act in a partially redundant manner to pattern the vertebrate limb. Biochemical screens probing the sequence specificity of the DNA-binding domains showed that HOX-TFs recognize largely similar DNA sequences, but also emphasized the important role of co-factors in HOX DNA-binding. However, due to their high sequence homology and overlapping expression patterns, little is known about the genome-wide binding of these transcription factors Here, we set out to systematically compare the effects of the nine limb-bud expressed HOX-TFs on cell differentiation and gene regulation, and compare their genome-wide binding characteristics. We find that HOX-TFs induce distinct regulatory programs in transduced cells. Through genome-wide DNA binding profiling we find that the posterior HOX-TFs can be separated into two groups with distinct binding motifs and association with co-factors. Through this unexpected grouping, we characterize the CCCTC-binding factor (CTCF) as a novel co-factor of HOX-TFs and show that one, but not the other group of HOX-TFs binds to thousands of CTCF-occupied sites in the chicken genome.
2016-12-31 | GSE85757 | GEO
Project description:Catalytic activity of the ISWI family of remodelers is critical for nucleosomal organization and transcription factor binding, including the insulator protein CTCF. To define which subcomplex mediates these diverse functions we phenotyped a panel of isogenic mouse stem cell lines each lacking one of six ISWI accessory subunits. Individual deletions of either CERF, RSF1, ACF, WICH or NoRC subcomplexes only moderately affect the chromatin landscape, while removal of the NURF-specific subunit BPTF leads to drastic reduction in chromatin accessibility and Snf2h ATPase localization around CTCF sites. While this reduces distances to the adjacent nucleosomes it only modestly impacts CTCF binding itself. In absence of accessibility, the insulator function of CTCF is nevertheless impaired resulting in lower occupancy of cohesin and cohesin-loading factors, and reduced insulation at these sites, highlighting the need of NURF-mediated remodeling for open chromatin and proper CTCF function. Our comprehensive analysis reveals a specific role for NURF in mediating Snf2h localization and chromatin opening at bound CTCF sites showing that local accessibility is critical for cohesin binding and insulator function.
2024-03-13 | PXD042945 | Pride
Project description:We sought to examine whether the non-canonical SMC protein Smchd1 plays a role in chromosome conformation. We used in situ Hi-C to analyse chromosome conformation changes upon deletion of the epigenetic regulator Smchd1 in female neural stem cells. In parallel, we analysed nucleosome accessibility using ATAC-seq, gene expression using RNA-seq, chromatin marks H3K27me3 and H3K27ac and Ctcf binding using ChIP-seq. We additionally analysed Smchd1 binding genome-wide using ChIP-seq. Together, we find that deletion of Smchd1 alters chromosome conformation at Smchd1 target genes including the inactive X chromosome, Hox genes and imprinted loci. Smchd1 deletion in differentiating ES cells results in failed Hox gene silencing and Smchd1 null E9.5 embryos show altered Hox gene expression.. Smchd1 deletion results in gain in Ctcf binding and activation of enhancers. We propose Smchd1 functions by limiting Ctcf-mediated chromosome looping.
2018-06-30 | GSE112041 | GEO
Project description:We sought to examine whether the non-canonical SMC protein Smchd1 plays a role in chromosome conformation. We used in situ Hi-C to analyse chromosome conformation changes upon deletion of the epigenetic regulator Smchd1 in female neural stem cells. In parallel, we analysed nucleosome accessibility using ATAC-seq, gene expression using RNA-seq, chromatin marks H3K27me3 and H3K27ac and Ctcf binding using ChIP-seq. We additionally analysed Smchd1 binding genome-wide using ChIP-seq. Together, we find that deletion of Smchd1 alters chromosome conformation at Smchd1 target genes including the inactive X chromosome, Hox genes and imprinted loci. Smchd1 deletion in differentiating ES cells results in failed Hox gene silencing. Smchd1 deletion results in gain in Ctcf binding and activation of enhancers. We propose Smchd1 functions by limiting Ctcf-mediated chromosome looping.
2018-06-30 | GSE111724 | GEO