Genome-wide Association of Yorkie with Chromatin and Chromatin-Remodeling Complexes

TY - JOUR

T1 - Genome-wide Association of Yorkie with Chromatin and Chromatin-Remodeling Complexes

AU - Oh, Hyangyee

AU - Slattery, Matthew

AU - Ma, Lijia

AU - Crofts, Alex

AU - White, Kevin P.

AU - Mann, Richard S.

AU - Irvine, Kenneth D.

N1 - Funding Information: We thank B. Hay, C.P. Verrijzer, T. Xu, the DSHB, and the Bloomington Stock Center for antibodies and Drosophila stocks; and Flybase, Dibyendu Kumar, and the Waksman Genomics Core for bioinformatics and sequencing support. This research was supported by HHMI and by NIH grants GM078620 (to K.D.I.), 5R01GM054510 (to R.S.M.), 5P50GM081892 (to K.P.W.), and 3U01HG004264 (to K.P.W.).

PY - 2013

Y1 - 2013

N2 - 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.

AB - 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.

UR - https://www.scopus.com/pages/publications/84874275439

UR - https://www.scopus.com/pages/publications/84874275439#tab=citedBy

U2 - 10.1016/j.celrep.2013.01.008

DO - 10.1016/j.celrep.2013.01.008

M3 - Article

C2 - 23395637

SN - 2211-1247

VL - 3

SP - 309

EP - 318

JO - Cell Reports

JF - Cell Reports

IS - 2

ER -