Abstract
BackgroundCGGBP1 is a repeat-binding protein with diverse functions in the regulation of gene expression, cytosine methylation, repeat silencing and genomic integrity. CGGBP1 has also been identified as a cooperator of histone-modifying enzymes and as a component of CTCF-containing complexes that regulate the enhancer–promoter looping. CGGBP1–CTCF cross talk in chromatin regulation has been hitherto unknown.ResultsHere, we report that the occupancy of CTCF at repeats depends on CGGBP1. Using ChIP-sequencing for CTCF, we describe its occupancy at repetitive DNA. Our results show that endogenous level of CGGBP1 ensures CTCF occupancy preferentially on repeats over canonical CTCF motifs. By combining CTCF ChIP-sequencing results with ChIP sequencing for three different kinds of histone modifications (H3K4me3, H3K9me3 and H3K27me3), we show that the CGGBP1-dependent repeat-rich CTCF-binding sites regulate histone marks in flanking regions.ConclusionCGGBP1 affects the pattern of CTCF occupancy. Our results posit CGGBP1 as a regulator of CTCF and its binding sites in interspersed repeats.
Highlights
Human CGGBP1 is a ubiquitously expressed protein with important functions in stress response, cell growth, proliferation and mitigation of endogenous DNA damage [1,2,3,4,5]
CGGBP1 and CTCF colocalize and interact with each other To study the possibilities of functional cross talk between CGGBP1 and CTCF, we tested the subcellular colocalization of the two proteins
Using immunofluorescence (IF) in human fibroblasts, we observed that endogenous CGGBP1 as well as CTCF predominantly localized to the nuclei (Fig. 1a and b)
Summary
Human CGGBP1 is a ubiquitously expressed protein with important functions in stress response, cell growth, proliferation and mitigation of endogenous DNA damage [1,2,3,4,5]. The CGGBP1 gene is conserved only in the amniotes with more than 98% similarity across the homeotherms [1]. The involvement of CGGBP1 in widely conserved cellular processes, such as cell cycle, maintenance of genomic integrity and cytosine methylation regulation, suggests that CGGBP1 fine-tunes these processes in homeothermic organisms to meet the challenges of their terrestrial habitats. CGGBP1 is a repeat-binding protein with diverse functions in the regulation of gene expression, cytosine methylation, repeat silencing and genomic integrity. CGGBP1–CTCF cross talk in chromatin regulation has been hitherto unknown
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