Ctcf binding site

Federal government websites often end in. The site is secure, ctcf binding site. CTCF has it all. The transcription factor binds to tens of thousands of genomic sites, some tissue-specific, others ultra-conserved.

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. The overwhelming majority of clustered CTCF sites colocalize with cohesin and are significantly closer to gene transcription start sites than nonclustered CTCF sites, suggesting that CTCF clusters particularly contribute to cohesin stabilization and transcriptional regulation.

Ctcf binding site

Federal government websites often end in. The site is secure. The eukaryotic genome is organized in the three-dimensional nuclear space in a specific manner that is both a cause and a consequence of its function. This organization is in part established by a special class of architectural proteins of which CTCF is the best characterized. Although CTCF has been assigned a variety of often contradictory roles, new results help draw a unifying model to explain the many functions of this protein. CTCF creates boundaries between topologically associating domains in chromosomes and, within these domains, CTCF facilitates interactions between transcription regulatory sequences. Thus, CTCF links the architecture of the genome to its function. Eukaryotic genomes are dynamically packaged into multiple levels of organization, from nucleosomes to chromatin fibers to large-scale chromosomal domains occupying defined territories of the nucleus. The three dimensional interplay of protein—DNA complexes facilitates timely realization of intricate nuclear functions such as transcription, replication, DNA repair and mitosis 1. A combination of microscopy and chromosome conformation capture 3C -related approaches 2 revealed that CCCTC-binding factor CTCF is in large part responsible for bridging the gap between nuclear organization and gene expression. CTCF is the main insulator protein described in vertebrates. Initially characterized as a transcription factor capable of activating or repressing gene expression in heterologous reporter assays 3 , 4 , CTCF was later found to display properties characteristic of insulators i. These properties, observed using transgene assays, were interpreted to suggest a role for insulators in restricting enhancer-promoter interactions and establishing functional domains of gene expression. In this Review, we discuss recent evidence, arising from the use of 3C-related techniques, indicating that the diverse properties of CTCF and other insulator proteins are based on their broader role in mediating inter- and intra-chromosomal interactions between distant sites in the genome.

Wang H, et al. CTCF is a ubiquitously expressed and an essential protein [ 1 ], and is, in many ways, an exceptional transcription factor.

Thank you for visiting nature. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser or turn off compatibility mode in Internet Explorer. In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript. It can function as a transcriptional activator, a repressor or an insulator protein, blocking the communication between enhancers and promoters.

Genome Biology volume 21 , Article number: Cite this article. Metrics details. An Author Correction to this article was published on 02 June However, it is also aberrantly expressed in many cancers. Finally, we reveal that the N, C, and zinc finger terminal domains play unique roles in targeting each paralog to distinct binding sites to regulate transcription, chromatin looping, and insulation. This study clarifies the unique and combined contribution of CTCF and CTCFL to chromosome organization and transcription, with direct implications for understanding how their co-expression deregulates transcription in cancer.

Ctcf binding site

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.

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The chromatin accessibility landscape of primary human cancers. Nuclear organization and genome function. Comprehensive identification and annotation of cell type-specific and ubiquitous CTCF-binding sites in the human genome. We found two interactions; one occurred Parelho, V. Most strikingly, it harbours insulator activity: when positioned in between an enhancer and gene promoter, it can block their communication and prevent transcriptional activation [ 5 — 7 ]. Yu M, et al. An oncogenic super-enhancer formed through somatic mutation of a noncoding intergenic element. Mol Brain ; 6 : Constitutively bound CTCF sites maintain 3D chromatin architecture and long-range epigenetically regulated domains.

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In addition, it is worth noting that motif occurrence alone is not enough for TF binding. Identification of CTCF-binding sequences that overlap a given CTCF-binding sequence: the database now contains CTCF-binding sites identified in many tissues and cell types in mice and humans, making it possible to investigate if CTCF binding is specific to a particular cell type or conserved and, potentially, help limit the location of a binding site to a more narrow range. In addition to identifying the topological domain location and binding motif type, each CTCF-binding sequence in the database is annotated with descriptions of the binding site and the experiment in which the site was identified Table 1. Identification of cancer-specific CTCF binding sites. We show that a significant fraction of species-specific CTCF sites also localizes in the vicinity of TAD borders and that CTCF binding sites at TAD boundaries have both stronger sequence constraints and stronger binding affinity, independent of their conservation across species. Elife 6 , 1—33 Nuclear organization and genome function. Table 1. Langmead, B. Wood AM, et al. For example, when CTCF and cohesin bind to their binding sites and create a chromatin loop that encompasses the enhancer and promoter, transcriptional activation occurs. CTCF and cohesin regulate chromatin loop stability with distinct dynamics. Ran, F. Array carried out by the Ramaciotti Centre for Genomics.