Analysis of non-methylated islands, sites of accessible chromatin and nascent transcriptome in C127 mouse cell line. [C127_BioCAP-ATAC-4sU]

Chromatin modifications and the promoter associated epigenome are thought to be important for the regulation of gene expression. However, the mechanisms by which chromatin modifying complexes are targeted to the appropriate gene promoters in vertebrates and how they influence gene expression have remained poorly defined. Here, using a combination of live cell imaging and functional genomics, we discover that the vertebrate SET1 complex is targeted to actively transcribed target gene promoters through CFP1 which engages in a unique form of multivalent chromatin reading that involves recognition of non-methylated DNA and histone H3 lysine 4 trimethylation (H3K4me3). CFP1 defines SET1 complex occupancy on chromatin and its multivalent interactions are required for the SET1 complex to place H3K4me3. In the absence of CFP1, gene expression is perturbed suggesting that the normal targeting and function of SET1 complex is central to creating an appropriately functioning vertebrate promoter associated epigenome. Overall design: C127 mouse cell line was employed to determine (i) genomic regions enriched for non-methylated DNA using BioCAP assay, (ii) genomic regions of accessible chromatin using ATAC-seq, (iii) nascent transcriptome using an in vivo pulse labelling with 4-thiouridine (4sU) followed by massively parallel sequencing (4sU-seq).