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.
Highlights
The mechanism by which protein complexes interact to regulate the deposition of post-translational modifications of histones remains poorly understood
We found that CFP1 is not solely recruited to CpG islands as it was originally defined, and other regions including non-CpG island promoters and enhancers
CFP1 primarily binds at active CpG islands (CGIs) transcription start sites (TSSs) and is associated with transcription We previously reported an association of CFP1 binding with transcription at the α-globin locus, using a mouse model in which the mouse α-globin locus was replaced by the human locus [29, 31]
Summary
The mechanism by which protein complexes interact to regulate the deposition of post-translational modifications of histones remains poorly understood This is 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, known as CGBP) is a subunit of the TrxG SET1 protein complex, a major catalyst of trimethylation of H3K4 (H3K4me). CpG dinucleotides are relatively depleted, except in specific DNA regions with a high density of this dinucleotide These regions are known as CpG islands (CGIs) and consist of short (~ 1000 bp) interspersed CpG-rich and predominantly unmethylated DNA sequences [1], which are associated with transcriptionally permissive chromatin state [2]. Two other TrxG complexes, MLL3 and MLL4, lack ZF-CxxC domains [10] and have been suggested to be involved in deposition of H3K4me at enhancer elements [18,19,20]
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