title: Yorkie promotes transcription by recruiting a histone methyltransferase complex.
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.
authors.affiliation: Howard Hughes Medical Institute, Waksman Institute and Department of Molecular Biology and Biochemistry, Rutgers University, Piscataway, NJ 08854, USA.
authors.forename: Hyangyee
authors.initials: H
authors.lastname: Oh
authors.affiliation: 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.
authors.forename: Matthew
authors.initials: M
authors.lastname: Slattery
authors.affiliation: Institute for Genomics and Systems Biology and Department of Human Genetics, University of Chicago, 900 East 57th Street, KCBD 10115, Chicago, IL 60637, USA.
authors.forename: Lijia
authors.initials: L
authors.lastname: Ma
authors.affiliation: Institute for Genomics and Systems Biology and Department of Human Genetics, University of Chicago, 900 East 57th Street, KCBD 10115, Chicago, IL 60637, USA.
authors.forename: Kevin P
authors.initials: KP
authors.lastname: White
authors.affiliation: Department of Biochemistry and Molecular Biophysics, Columbia University, 701 West 168th Street, HHSC 1104, New York, NY 10032, USA.
authors.forename: Richard S
authors.initials: RS
authors.lastname: Mann
authors.affiliation: 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.
authors.forename: Kenneth D
authors.initials: KD
authors.lastname: Irvine
mesh_terms: D020816:Amino Acid Motifs; D000818:Animals; D001665:Binding Sites; D002843:Chromatin / Q000235:genetics / Q000378:metabolism; D004330:Drosophila / Q000235:genetics* / Q000378:metabolism; D029721:Drosophila Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D009687:Nuclear Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D056918:Nuclear Receptor Coactivators / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D015534:Trans-Activators / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation; D000091102:YAP-Signaling Proteins
chemical_list: D002843:Chromatin; D029721:Drosophila Proteins; C000599734:Ncoa6 protein, Drosophila; D009687:Nuclear Proteins; D056918:Nuclear Receptor Coactivators; D015534:Trans-Activators; D000091102:YAP-Signaling Proteins; C503814:Yki protein, Drosophila