CTCF: the protein, the binding partners, the binding sites and their chromatin loops

Abstract

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. Yet, or perhaps therefore, CTCF's exact function at a given genomic site is unpredictable. It appears to be determined by the associated transcription factors, by the location of the binding site relative to the transcriptional start site of a gene, and by the site's engagement in chromatin loops with other CTCF-binding sites, enhancers or gene promoters. Here, we will discuss genome-wide features of CTCF binding events, as well as locus-specific functions of this remarkable transcription factor.

Active chromatin and transcription play a key role in chromosome partitioning into topologically associating domains

“…We note that disruption of the cohesin/CTCF complex in mammals, as well as depletion of the Vtd (also known as Rad21) cohesin subunit in Drosophila, did not lead to disappearance of TAD boundaries, but rather only slightly decreased interactions inside TADs (in mammals) and reduced TAD boundary strength in the Drosophila genome (Sofueva et al 2013;Li et al 2015). These observations favor a role for the cohesin/CTCF complex, which is known to form loops (Splinter et al 2006;Holwerda and de Laat 2013), in chromatin compaction inside the TADs.…”

Combining transcription factor binding affinities with open-chromatin data for accurate gene expression prediction

“…The TF GATA4 was shown to be involved in liver 424 induction [2]. CTCF was found to have a role in imprinting liver [23,28], and NRF1 425 has a protective function against oxidative stress in liver [68].…”

“…a third of known human 26 developmental disorders are related to deregulated TFs [64]. 27 Several general approaches have been proposed to identify TFs acting as key players 28 in gene regulation depending on the available data: Coexpression analysis combined 29 with computational predictions of TF sequence binding can be used to identify key 30 TFs [18]. Genome-wide TF binding data, as produced by TF ChIP-seq, is widely used 31 to identify important TFs: ChIP-seq data was incorporated into coexpression 32 analysis [43], was combined with transcriptome data [49,66], used for the construction 33 of Gene Regulatory Networks (GRNs) [8], and used together with Hi-C data [40].…”

Chromatin Domain Organization of the TCRb Locus and Its Perturbation by Ectopic CTCF Binding

“…Subsequently, CTCF has emerged as an important architectural protein that can influence interchromosomal and intrachromosomal interactions and impact nuclear functions largely in collaboration with cohesin (4,5). Genome-wide investigations, including chromatin immunoprecipitation (ChIP), 4C, Hi-C, and chromatin interaction analysis by paired-end tag sequencing (ChIA-PET), etc., have established an important role of CTCF in organization of topologically associated domains (TADs) (6,7). In addition, CTCF binding sites (CBS) located within TADs can contribute to celltype-specific chromatin loop organization by facilitating, as well as inhibiting, the interactions between regulatory elements.…”