Yorkie promotes transcription by recruiting a histone methyltransferase complex

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

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Motifs
  • Animals
  • Binding Sites
  • Chromatin / genetics
  • Chromatin / metabolism
  • Drosophila / genetics*
  • Drosophila / metabolism
  • Drosophila Proteins / chemistry
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism*
  • Nuclear Proteins / chemistry
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • Nuclear Receptor Coactivators / chemistry
  • Nuclear Receptor Coactivators / genetics
  • Nuclear Receptor Coactivators / metabolism*
  • Protein Binding
  • Trans-Activators / chemistry
  • Trans-Activators / genetics
  • Trans-Activators / metabolism*
  • Transcriptional Activation*
  • YAP-Signaling Proteins

Substances

  • Chromatin
  • Drosophila Proteins
  • Ncoa6 protein, Drosophila
  • Nuclear Proteins
  • Nuclear Receptor Coactivators
  • Trans-Activators
  • YAP-Signaling Proteins
  • Yki protein, Drosophila

Associated data

  • GEO/GSE38594
  • GEO/GSE46305