Global analysis of the insulator binding protein CTCF in chromatin barrier regions reveals demarcation of active and repressive domains.

By Suresh Cuddapah, R. Jothi, Dustin E. Schones, Tae-Young Roh, Kairong Cui, Keji Zhao. Genome Research, 2008

670 citations recorded by the source corpus.

Insulators are DNA elements that prevent inappropriate interactions between the neighboring regions of the genome. They can be functionally classified as either enhancer blockers or domain barriers. CTCF (CCCTC-binding factor) is the only known major insulator-binding protein in the vertebrates and has been shown to bind many enhancer-blocking elements. However, it is not clear whether it plays a role in chromatin domain barriers between active and repressive domains. Here, we used ChIP-seq to map the genome-wide binding sites of CTCF in three cell types and identified significant binding of CTCF to the boundaries of repressive chromatin domains marked by H3K27me3. Although we find an extensive overlapping of CTCF-binding sites across the three cell types, its association with the domain boundaries is cell-type-specific. We further show that the nucleosomes flanking CTCF-binding sites are well positioned. Interestingly, we found a complementary pattern between the repressive H3K27me3 and the active H2AK5ac regions, which are separated by CTCF. Our data indicate that CTCF may play important roles in the barrier activity of insulators, and this study provides a resource for further investigation of the CTCF function in organizing chromatin in the human genome.

Subfields: Genetics, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/390c0fcfa30467505a601eac9f48117daa1c00d2

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Genetics

In Molecular Biology

Citations in the corpus

YY1 Is a Structural Regulator of Enhancer-Promoter Loops (2017, positive): “, 2006), but CTCF does not generally occupy these interacting elements (Cuddapah et al., 2009; Kim et al., 2007; Phillips-Cremins et al., 2013; Wendt et al., 2008).”
Distinct Epigenomic Landscapes of Pluripotent and Lineage-committed Human Cells (2010, methodology): “We analyzed genomewide profiles of H3K27me3 in CD4 T cells (Barski et al., 2007; Cuddapah et al., 2009).”
Comprehensive Genome-wide Protein-DNA Interactions Detected at Single Nucleotide Resolution (2011, background): “Estimates range from 13,000 to 29,000 binding locations across mammalian genomes (Cuddapah et al., 2009; Dion et al., 2007).”
Targeted degradation of CTCF decouples local insulation of chromosome domains from genomic compartmentalization (2017, neutral): “As reported in human cells (Cuddapah et al., 2009), we found that a subset of CTCF sites mark transitions in H3K27me3 enrichment in mESCs (∼7% of CTCF sites, Figure 7A).”
CTCF: Master Weaver of the Genome (2009, positive): “19,572 in HeLa and Jurkat cells, respectively (Cuddapah et al., 2009).”
A three-dimensional map of the human genome at kilobase resolution reveals principles of chromatin looping (2014, positive): “Because many of our loops demarcate domains, this observation is also consistent with studies suggesting that CTCF delimits structural and regulatory domains (Xie et al., 2007; Cuddapah et al., 2009; Dixon et al., 2012).”
High-resolution genome-wide DNA methylation maps of mouse primary female dermal fibroblasts and keratinocytes (2014, neutral): “CTCF is a zinc finger protein initially known for its insulating properties at the beta globin locus [45-47].”
CTCF-Mediated Functional Chromatin Interactome in Pluripotent Cells (2011, background): “To address its function as an insulator-binding protein, CTCF binding profiles have been determined from the genomes of several different cell types and across specie”
Widespread plasticity in CTCF occupancy linked to DNA methylation (2012, positive): “This study exposes a previously unappreciated degree of plasticity within the binding landscape of the master genomic regulator CTCF. Previous studies in a small number of cell types had un-coveredonlylimitedcell-typespecificity(Kimetal.2007;Cuddapah et al. 2008; Heintzman et al. 2009).”
Regions of focal DNA hypermethylation and long-range hypomethylation in colorectal cancer coincide with nuclear lamina–associated domains (2011, background): “Similarly, methylation-resistant elements had 29× enrichment for CTCF insulator binding site”
A computational pipeline for comparative ChIP-seq analyses (2011, background): “As data on insulator protein binding sites are now available (e.g., for the Drosophila 23 , mouse 13 and human 24 genomes), gene assignment can be prohibited across insulator sites.”
Control of cell identity genes occurs in insulated neighborhoods in mammalian chromosomes (2014, positive): “The mechanisms responsible for maintaining the H3K27me3 mark across short spans of regulatory regions and promoters of repressed genes are not well understood, although CTCF sites have been implicated (Cuddapah et al., 2009; Schwartz et al., 2012; Van Bortle et al., 2012).”
Genome-wide mapping of nucleosome positioning and DNA methylation within individual DNA molecules (2012, methodology): “2007) or CD4+ T-cells (Figs. 2B, 3A, GBM; Cuddapah et al. 2009) and those obtained using ChIP-seq in IMR90 cells from GEO record GSM935404 (Fig.”