CTCF, cohesin, and histone variants: Connecting the genome

Department of Biology, Faculty of Sciences, Université de Sherbrooke, Sherbrooke, QC J1K 2R1, Canada.
Biochemistry and Cell Biology (Impact Factor: 2.15). 10/2011; 89(5):505-13. DOI: 10.1139/o11-052
Source: PubMed


During the last decades our view of the genome organization has changed. We moved from a linear view to a looped view of the genome. It is now well established that inter- and intra-connections occur between chromosomes and play a major role in gene regulations. These interconnections are mainly orchestrated by the CTCF protein, which is also known as the "master weaver" of the genome. Recent advances in sequencing and genome-wide studies revealed that CTCF binds to DNA at thousands of sites within the human genome, providing the possibility to form thousands of genomic connection hubs. Strikingly, two histone variants, namely H2A.Z and H3.3, strongly co-localize at CTCF binding sites. In this article, we will review the recent advances in CTCF biology and discuss the role of histone variants H2A.Z and H3.3 at CTCF binding sites.

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Available from: Jean-Francois Millau, Jun 23, 2014
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    • "Based on these evidences, it is easy to realize that transacting factors and cis-acting elements play vital roles in regulating nearby-gene expression and maintaining genome topology. The identification of individual basal components, especially various TFs and protein markers, makes people used to judge gene regulatory network as protein-centric, which is depending on protein-mediated transcriptional control (Millau and Gaudreau, 2011). However, as Dr. "
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    • "Also identified as specific to the RNAPII complex were chromatin-associated proteins including CTCF, SAFB2, and histone methyltranferases EZH2, SUV39H1, and SUV39H2 (Melnik et al. 2011). CTCF is a transcriptional regulator associated with insulator activity and points of chromatin–chromatin looping interactions (Handoko et al. 2011; Millau and Gaudreau, 2011). SAFB2 is a scaffold attachment factor highly homologous to SAFB1 that binds scaffold/matrix attachment regions (S/MAR) of DNA and also functions as a transcriptional corepressor (Townson et al. 2003; Townson et al. 2004). "
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    • "Thus, DNp63a promotes H2A.Z deposition, possibly through a mechanism that involves gene looping from the enhancer to the promoter. Given that H2A.Z has been found to colocalize with CTCF to bridge and loop DNA (Millau and Gaudreau 2011), it is not necessarily surprising that the DNp63a-specific deposition of H2A.Z may be mediated by the action of these subunits at the distal enhancer site. Of note, DNp63a knockdown also causes decreased occupancy of DMAP1 and RUVBL2 at the enhancers of the class III genes NTN4, SAMD9L, and IGFBP3 as well as reduced H2A.Z signals at the promoters of NTN4 and SAMD9L (Supplemental Fig. 12). "
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