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
Affiliations
David A. Brown
Department of Biochemistry, University of Oxford, Oxford, OX1 3QU, UK
Vincenzo Di Cerbo
Department of Biochemistry, University of Oxford, Oxford, OX1 3QU, UK
Angelika Feldmann
Department of Biochemistry, University of Oxford, Oxford, OX1 3QU, UK
Jaewoo Ahn
Department of Pharmacology, University of Colorado School of Medicine, Aurora, CO 80045, USA
Shinsuke Ito
Laboratory for Developmental Genetics, RIKEN Center for Integrative Medical Sciences (IMS), 1-7-2 Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan
Neil P. Blackledge
Department of Biochemistry, University of Oxford, Oxford, OX1 3QU, UK
Manabu Nakayama
Laboratory for Developmental Genetics, RIKEN Center for Integrative Medical Sciences (IMS), 1-7-2 Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan
Michael McClellan
Ludwig Cancer Research, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7DQ, UK
Emilia Dimitrova
Department of Biochemistry, University of Oxford, Oxford, OX1 3QU, UK
Anne H. Turberfield
Department of Biochemistry, University of Oxford, Oxford, OX1 3QU, UK
Hannah K. Long
Department of Biochemistry, University of Oxford, Oxford, OX1 3QU, UK
Hamish W. King
Department of Biochemistry, University of Oxford, Oxford, OX1 3QU, UK
Skirmantas Kriaucionis
Ludwig Cancer Research, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7DQ, UK
Lothar Schermelleh
Department of Biochemistry, University of Oxford, Oxford, OX1 3QU, UK
Tatiana G. Kutateladze
Department of Pharmacology, University of Colorado School of Medicine, Aurora, CO 80045, USA
Haruhiko Koseki
Laboratory for Developmental Genetics, RIKEN Center for Integrative Medical Sciences (IMS), 1-7-2 Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan
Robert J. Klose
Department of Biochemistry, University of Oxford, Oxford, OX1 3QU, UK
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.
