Ctcf binding site

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Genome Biology volume 21 , Article number: 5 Cite this article. Metrics details. CTCF binding contributes to the establishment of a higher-order genome structure by demarcating the boundaries of large-scale topologically associating domains TADs. We carry out an experimental and computational study that exploits the natural genetic variation across five closely related species to assess how CTCF binding patterns stably fixed by evolution in each species contribute to the establishment and evolutionary dynamics of TAD boundaries. Our analyses reveal that CTCF binding is maintained at TAD boundaries by a balance of selective constraints and dynamic evolutionary processes. TAD boundaries frequently harbor dynamically evolving clusters containing both evolutionarily old and young CTCF sites as a result of the repeated acquisition of new species-specific sites close to conserved ones.

Ctcf binding site

The authors wish it to be known that, in their opinion, the first two authors should be regarded as joint First Authors. Jesse D. CTCF is a highly conserved transcriptional regulator protein that performs diverse functions such as regulating gene expression and organizing the 3D structure of the genome. Since the original publication of the database, studies of the 3D structure of the genome, such as those provided by Hi-C experiments, have suggested that CTCF plays an important role in mediating intra- and inter-chromosomal interactions. To reflect this important progress, we have integrated CTCF-binding sites with genomic topological domains defined using Hi-C data. Additionally, the updated database includes new features enabled by new CTCF-binding site data, including binding site occupancy and the ability to visualize overlapping CTCF-binding sites determined in separate experiments. A few years ago, several groups attempted to better characterize CTCF function by identifying human and mouse CTCF-binding sites genome wide using both experimental and computational methods 5—8. Additionally, these datasets of CTCF-binding sites were used to establish that, while many functional CTCF-binding sites do not match a consensus motif 9 , there is a CTCF-binding site motif that is highly conserved in vertebrates 5. The initial version of CTCFBSDB contained 34 experimental and 18 predicted CTCF-binding sequences and integrated these sites with functional annotations and gene expression profiles to examine how the binding sites may provide insulator function. Specifically, CTCF-binding sites were found to be significantly overrepresented both on Hi-C fragments that had a large number of long-range interactions 13 and at the boundaries of the topological domains that spatially organize the genome In parallel with this changing understanding of the importance of CTCF, there has been remarkable growth in the number of experimentally identified CTCF-binding sites.

CTCF: master weaver of the genome.

Federal government websites often end in. The site is secure. CTCF has it all. The transcription factor binds to tens of thousands of genomic sites, some tissue-specific, others ultra-conserved. It can act as a transcriptional activator, repressor and insulator, and it can pause transcription. CTCF binds at chromatin domain boundaries, at enhancers and gene promoters, and inside gene bodies. It can attract many other transcription factors to chromatin, including tissue-specific transcriptional activators, repressors, cohesin and RNA polymerase II, and it forms chromatin loops.

We collected position weight matrices of CTCF binding motifs and defined strand-oriented CTCF binding sites in the human and mouse genomes, including the recent Telomere to Telomere and mm39 assemblies. Our comprehensive data resource and usage recommendations can serve to harmonize and strengthen the reproducibility of genomic studies utilizing CTCF binding data. Supplementary data are available at Bioinformatics Advances online. The structural and regulatory organization of the mammalian genome is fundamentally dependent on CTCF CCCTC-binding factor , a versatile transcription regulator evolutionary conserved from fruit fly to human Kim et al. It has been found to be involved in a variety of regulatory functions including transcriptional activation, imprinting, X-chromosome activation, cancer and developmental disorders, and chromatin interactions in three dimensions Ohlsson et al. CTCF binds DNA through the combinatorial use of its zinc-finger domains to target sites with remarkable sequence variation Jolma et al. The complexity of CTCF binding was also noted in the earlier study of motif discovery in conserved noncoding elements by Xie et al. CTCF binding is generally conserved between different tissues Kim et al. We aimed to provide uniformly detected strand-specific CTCF binding sites for human and mouse genomes, generally applicable for any cell type.

Ctcf binding site

CTCF is a highly conserved transcriptional regulator protein that performs diverse functions such as regulating gene expression and organizing the 3D structure of the genome. Since the original publication of the database, studies of the 3D structure of the genome, such as those provided by Hi-C experiments, have suggested that CTCF plays an important role in mediating intra- and inter-chromosomal interactions. To reflect this important progress, we have integrated CTCF-binding sites with genomic topological domains defined using Hi-C data.

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Our data also indicate that the boundaries of TADs commonly overlap with Mus -conserved CTCF sites, similar to observations from more distantly related mammalian lineages [ 10 , 37 ]. Conversely, CTCF cannot bind the paternal ICR because it is methylated, 17 and thus, the enhancer is able to activate Igf2 transcription from the paternal chromosome Figure 1. Cell Reports. The human enhancer blocker CTC-binding factor interacts with the transcription factor Kaiso. HTSeq--a Python framework to work with high-throughput sequencing data. Cohesins form chromosomal cis-interactions at the developmentally regulated IFNG locus. Sorry, a shareable link is not currently available for this article. Advanced search. A complex chromatin landscape revealed by patterns of nuclease sensitivity and histone modification within the mouse beta-globin locus. The latter may well be true, because 5C chromosome conformation capture carbon copy technology showed that most CTCF sites across 1 per cent of the genome do not participate in chromatin loops, no matter whether they are co-occupied by cohesin or not. Comments 0. Biochem Biophys Res Commun. Importantly, for all CTCF binding sites, including species-specific ones, proximity to a TAD boundary was associated with an increase in binding affinity Fig. Insulator dysfunction and oncogene activation in IDH mutant gliomas.

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This suggests that clusters of closely located CTCF binding sites help stabilize cohesin and may represent anchors of chromatin loops or TAD boundaries. As the eukaryotic genome is packaged through several levels of organization, its three-dimensional organization is closely related to how genes are expressed. Thyroid hormone-regulated enhancer blocking: cooperation of CTCF and thyroid hormone receptor. The human enhancer blocker CTC-binding factor interacts with the transcription factor Kaiso. The contact maps were visualized using Juicebox [ 83 ]. Fullwood MJ, et al. Pairwise comparison between two cell types revealed that it is mostly the CTCF-independent cohesin-binding events that show cell-type specificity. Hoxd gene expression in the limb bud is under the control of many distant regulatory sequences that physically loop towards the genes [ 69 ]. S1d, green :. Langmead B, Salzberg SL. Single-cell hi-C reveals cell-to-cell variability in chromosome structure. For human and mouse, the database contains CTCF-binding sequences identified in many cell types and experiments. CTCF binding and remodeling of the three-dimensional structure of the genome Accumulating evidence shows that CTCF aids long-range chromosomal interactions via looping. This process apparently facilitates gene transcription by allowing RNA polymerase II to push cohesin along gene bodies [ 57 , 58 , 59 ]. Download citation.