CpG binding protein (CFP1) occupies open chromatin regions of active genes, including enhancers and non-CpG islands

Abstract

BackgroundThe mechanism by which protein complexes interact to regulate the deposition of post-translational modifications of histones remains poorly understood. This is particularly important at regulatory regions, such as CpG islands (CGIs), which are known to recruit Trithorax (TrxG) and Polycomb group proteins. The CxxC zinc finger protein 1 (CFP1, also known as CGBP) is a subunit of the TrxG SET1 protein complex, a major catalyst of trimethylation of H3K4 (H3K4me3).ResultsHere, we used ChIP followed by high-throughput sequencing (ChIP-seq) to analyse genomic occupancy of CFP1 in two human haematopoietic cell types. We demonstrate that CFP1 occupies CGIs associated with active transcription start sites (TSSs), and is mutually exclusive with H3K27 trimethylation (H3K27me3), a marker of polycomb repressive complex 2. Strikingly, rather than being restricted to active CGI TSSs, CFP1 also occupies a substantial fraction of active non-CGI TSSs and enhancers of transcribed genes. However, relative to other TrxG subunits, CFP1 was specialised to TSSs. Finally, we found enrichment of CpG-containing DNA motifs in CFP1 peaks at CGI promoters.ConclusionsWe found that CFP1 is not solely recruited to CpG islands as it was originally defined, but also other regions including non-CpG island promoters and enhancers.Electronic supplementary materialThe online version of this article (10.1186/s13072-018-0230-0) contains supplementary material, which is available to authorized users.

The glucocorticoid receptor recruits the COMPASS complex to regulate inflammatory transcription at macrophage enhancers

“…CXXC1 occupancy was similar to SETD1A, with enhancers gaining SETD1A also gaining CXXC1 and enhancers losing SETD1A also losing CXXC1 binding ( Figure S3 D). This co-dependency of SETD1A and CXXC1 recruitment is consistent with their known function within the same complex and with the observation that CXXC1 is required for SETD1A recruitment at promoters ( Brown et al., 2017 ; van de Lagemaat et al., 2018 ).…”

“…Our observations of SETD1A/COMPASS enhancer occupancy agree with recent studies on accessible regions in erythrocytes and on MEF2-marked neuronal enhancers ( van de Lagemaat et al., 2018 ; Mukai et al., 2019 ). These results challenge earlier views that SETD1A/COMPASS is exclusively recruited to promoters, as described in yeast and Drosophila ( Ng et al., 2003 ; Ardehali et al., 2011 ).…”

“…Altogether, GR, SETD1A, and, to a lesser extent, CXXC1 co-occupy genomic loci in macrophages treated with Dex + LPS. These common cis -regulatory regions were mostly intergenic, demonstrating that the SETD1A/COMPASS complex is bound to mammalian enhancers in vivo ( van de Lagemaat et al., 2018 ; Mukai et al., 2019 ). However, this co-occupancy only represents a fraction of the GR cistrome, indicating that diverse functional classes or categories of regulatory sites likely exist.…”

Sequence features of retrotransposons allow for epigenetic variability

“…The CpG content of VM-IAPLTRs, however, is similar to non-VM-IAPLTRs, indicating that high CpG content alone is not sufficient to induce variable methylation (Figure 3B). As CpG dense loci are capable of being recognized and bound by ZF-CxxC proteins (Clouaire et al, 2012;Gu et al, 2018;Long et al, 2013;van de Lagemaat et al, 2018), we utilized a publicly available ChIP-seq dataset for the ZF-CxxC-domain containing protein TET1 in ES cells (Gu et al, 2018) to examine ZF-CxxC binding across all IAPLTR1s. We identified increased TET1 binding at clade3 IAPLTR1s elements, which is enriched for VM-IAPs (Figure 3C).…”

The survival analysis and oncogenic effects of CFP1 and 14-3-3 expression on gastric cancer

“…The CXXC zinc finger protein 1 (CFP1, also known as CGBP) is a subunit of the TrxG SET1 protein complex, a major catalyst of histone 3 lysine 4 trimethylation (H3K4me3) [18, 19]. CFP1 binds to DNA via its CXXC finger domain and its PHD domain, and recruits SETD1 to the promoter of actively transcribed CGI-related genes [20].…”