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Cell Rep. 2017 Sep 5;20(10):2313-2327. doi: 10.1016/j.celrep.2017.08.030.

The SET1 Complex Selects Actively Transcribed Target Genes via Multivalent Interaction with CpG Island Chromatin.

Author information

1
Department of Biochemistry, University of Oxford, Oxford, OX1 3QU, UK.
2
Department of Pharmacology, University of Colorado School of Medicine, Aurora, CO 80045, USA.
3
Laboratory for Developmental Genetics, RIKEN Center for Integrative Medical Sciences (IMS), 1-7-2 Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan.
4
Ludwig Cancer Research, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7DQ, UK.
5
Department of Biochemistry, University of Oxford, Oxford, OX1 3QU, UK. Electronic address: rob.klose@bioch.ox.ac.uk.

Abstract

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.

KEYWORDS:

CpG island; DNA methylation; H3K4me3; SET1; chromatin; epigenetics; histone; histone methylation; multivalent; transcription

PMID:
28877467
PMCID:
PMC5603731
DOI:
10.1016/j.celrep.2017.08.030
[Indexed for MEDLINE]
Free PMC Article

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