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Cell Rep. 2014 Jul 24;8(2):449-59. doi: 10.1016/j.celrep.2014.06.017. Epub 2014 Jul 10.

Yorkie promotes transcription by recruiting a histone methyltransferase complex.

Author information

1
Howard Hughes Medical Institute, Waksman Institute and Department of Molecular Biology and Biochemistry, Rutgers University, Piscataway, NJ 08854, USA.
2
Department of Biochemistry and Molecular Biophysics, Columbia University, 701 West 168th Street, HHSC 1104, New York, NY 10032, USA; Institute for Genomics and Systems Biology and Department of Human Genetics, University of Chicago, 900 East 57th Street, KCBD 10115, Chicago, IL 60637, USA.
3
Institute for Genomics and Systems Biology and Department of Human Genetics, University of Chicago, 900 East 57th Street, KCBD 10115, Chicago, IL 60637, USA.
4
Department of Biochemistry and Molecular Biophysics, Columbia University, 701 West 168th Street, HHSC 1104, New York, NY 10032, USA.
5
Howard Hughes Medical Institute, Waksman Institute and Department of Molecular Biology and Biochemistry, Rutgers University, Piscataway, NJ 08854, USA. Electronic address: irvine@waksman.rutgers.edu.

Abstract

Hippo signaling limits organ growth by inhibiting the transcriptional coactivator Yorkie. Despite the key role of Yorkie in both normal and oncogenic growth, the mechanism by which it activates transcription has not been defined. We report that Yorkie binding to chromatin correlates with histone H3K4 methylation and is sufficient to locally increase it. We show that Yorkie can recruit a histone methyltransferase complex through binding between WW domains of Yorkie and PPxY sequence motifs of NcoA6, a subunit of the Trithorax-related (Trr) methyltransferase complex. Cell culture and in vivo assays establish that this recruitment of NcoA6 contributes to Yorkie's ability to activate transcription. Mammalian NcoA6, a subunit of Trr-homologous methyltransferase complexes, can similarly interact with Yorkie's mammalian homolog YAP. Our results implicate direct recruitment of a histone methyltransferase complex as central to transcriptional activation by Yorkie, linking the control of cell proliferation by Hippo signaling to chromatin modification.

PMID:
25017066
PMCID:
PMC4152371
DOI:
10.1016/j.celrep.2014.06.017
[Indexed for MEDLINE]
Free PMC Article

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