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

The 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).

Here, 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.

We 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.