Genome-wide association of Yorkie with chromatin and chromatin-remodeling complexes

Cell Rep. 2013 Feb 21;3(2):309-18. doi: 10.1016/j.celrep.2013.01.008. Epub 2013 Feb 8.

Abstract

The Hippo pathway regulates growth through the transcriptional coactivator Yorkie, but how Yorkie promotes transcription remains poorly understood. We address this by characterizing Yorkie's association with chromatin and by identifying nuclear partners that effect transcriptional activation. Coimmunoprecipitation and mass spectrometry identify GAGA factor (GAF), the Brahma complex, and the Mediator complex as Yorkie-associated nuclear protein complexes. All three are required for Yorkie's transcriptional activation of downstream genes, and GAF and the Brahma complex subunit Moira interact directly with Yorkie. Genome-wide chromatin-binding experiments identify thousands of Yorkie sites, most of which are associated with elevated transcription, based on genome-wide analysis of messenger RNA and histone H3K4Me3 modification. Chromatin binding also supports extensive functional overlap between Yorkie and GAF. Our studies suggest a widespread role for Yorkie as a regulator of transcription and identify recruitment of the chromatin-modifying GAF protein and BRM complex as a molecular mechanism for transcriptional activation by Yorkie.

Publication types

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

MeSH terms

  • Animals
  • Cell Cycle Proteins / metabolism
  • Chromatin / metabolism*
  • Chromatin Assembly and Disassembly*
  • DNA-Binding Proteins / antagonists & inhibitors
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Drosophila / genetics
  • Drosophila Proteins / antagonists & inhibitors
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism*
  • Genome*
  • Histones / metabolism
  • Mediator Complex / metabolism
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • Protein Binding
  • RNA Interference
  • RNA, Messenger / analysis
  • RNA, Small Interfering / metabolism
  • Trans-Activators / genetics
  • Trans-Activators / metabolism*
  • Transcription Factors / antagonists & inhibitors
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Transcriptional Activation
  • Wings, Animal / pathology

Substances

  • Cell Cycle Proteins
  • Chromatin
  • DNA-Binding Proteins
  • Drosophila Proteins
  • Histones
  • Mediator Complex
  • Nuclear Proteins
  • RNA, Messenger
  • RNA, Small Interfering
  • Trans-Activators
  • Transcription Factors
  • Trl protein, Drosophila
  • Yki protein, Drosophila
  • brm protein, Drosophila
  • mor protein, Drosophila

Associated data

  • GEO/GSE38594