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

Genome Biology volume 21 , Article number: Cite this article. Metrics details. The three-dimensional genome organization is critical for gene regulation and can malfunction in diseases like cancer. Among the prolific binding sites in the genome, several events with altered CTCF occupancy have been reported as associated with effects in physiology or disease. However, hitherto there is no comprehensive survey of genome-wide CTCF binding patterns across different human cancers. We show that cancer-specific lost and gained CTCF binding events are associated with altered chromatin interactions, partially with DNA methylation changes, and rarely with sequence mutations. While lost bindings primarily occur near gene promoters, most gained CTCF binding events exhibit enhancer activities and are induced by oncogenic transcription factors. We validate these findings in T cell acute lymphoblastic leukemia cell lines and patient samples and show that oncogenic NOTCH1 induces specific CTCF binding and they cooperatively activate expression of target genes, indicating transcriptional condensation phenomena. Specific CTCF binding events occur in human cancers. Cancer-specific CTCF binding can be induced by other transcription factors to regulate oncogenic gene expression. Our results substantiate CTCF binding alteration as a functional epigenomic signature of cancer.

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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.

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.

Ctcf binding site

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To date, the role of CTCF in determining 3D genome organization has been considered mostly in the context of its effect on transcription during G1 but both the protein and the architectural properties of the genome it controls are likely to be also important at other stages of the cell cycle, including DNA replication during S phase and chromosome condensation during mitosis Or does insulation involve the physical interaction of the insulator sequence with both enhancers and promoters? Kagey MH, et al. Dynamic long-range chromatin interactions control Myb proto-oncogene transcription during erythroid development. Blue shadow boxes highlight the statistically significant peaks identified by MACS, while pink shadow boxes mark CTCF binding losses orthologous regions with no significant peaks. SK is supported by a BK21 fellowship. In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript. S1d to determine the cutoff for constitutive CTCF sites. We concluded that a considerable portion of cancer-specific CTCF binding alteration events associate with DNA methylation change in the binding regions. Cell Systems ;3 1 — Our data also reveal discrepancies in the expansion of TE classes at TAD boundary regions compared to the background genome. Again, chromatin loops are formed and seem important for ICR functioning [ 24 — 26 ].

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CTCF, chromatin loops and transcription regulation at selected gene loci. Song CX, et al. Figure 3. Figure 2. Open in a separate window. Cell , — USA 99 , — Irizarry, R. International network of cancer genome projects. Seitan VC, et al. Stable CTCF binding is highly specific to the presence of its DNA-binding motif and can be compromised by mutations affecting the consensus motif sequence [ 20 , 30 ]. Additionally, the CTCF gene itself or its binding sequence can be mutated and has been suggested to be a haploinsufficient tumor suppressor [ 12 ]. Finally, we investigated whether the evolutionary characteristics of clustered CTCF binding across the five species were recapitulated when looking at a single species. Show results from All journals This journal. USA , 17 —17