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

David A Brown, Vincenzo Di Cerbo, Angelika Feldmann, Jaewoo Ahn, Shinsuke Ito, Neil P Blackledge, Manabu Nakayama, Michael McClellan, Emilia Dimitrova, Anne H Turberfield, Hannah K Long, Hamish W King, Skirmantas Kriaucionis, Lothar Schermelleh, Tatiana G Kutateladze, Haruhiko Koseki, Robert J Klose

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

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 languageEnglish
Pages (from-to)2313-2327
Number of pages15
JournalCell Reports
Volume20
Issue number10
DOIs
Publication statusPublished - 5 Sept 2017

Keywords / Materials (for Non-textual outputs)

  • Animals
  • Chromatin/metabolism
  • Chromatin Immunoprecipitation
  • CpG Islands/genetics
  • DNA Methylation/genetics
  • Fluorescence Recovery After Photobleaching
  • Histones/metabolism
  • Humans
  • Methylation
  • Promoter Regions, Genetic/genetics
  • Spectrometry, Fluorescence

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