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Chromatin modifications and the promoter-associated epigenome are 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 gene promoters through CFP1, which engages in a 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 normal targeting and function of the SET1 complex are central to creating an appropriately functioning vertebrate promoter-associated epigenome.

Original publication

DOI

10.1016/j.celrep.2017.08.030

Type

Journal article

Journal

Cell Rep

Publication Date

05/09/2017

Volume

20

Pages

2313 - 2327

Keywords

CpG island, DNA methylation, H3K4me3, SET1, chromatin, epigenetics, histone, histone methylation, multivalent, transcription, Animals, Chromatin, Chromatin Immunoprecipitation, CpG Islands, DNA Methylation, Fluorescence Recovery After Photobleaching, Histones, Humans, Methylation, Promoter Regions, Genetic, Spectrometry, Fluorescence