Yorkie Promotes Transcription by Recruiting a Histone Methyltransferase Complex

Hyangyee Oh, Matthew Slattery, Lijia Ma, Kevin P. White, Richard S. Mann, Kenneth D. Irvine

Research output: Contribution to journalArticlepeer-review

36 Scopus citations

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 invivo 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.

Original languageEnglish (US)
Pages (from-to)449-459
Number of pages11
JournalCell reports
Volume8
Issue number2
DOIs
StatePublished - Jul 24 2014

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