PgmNr D1092: Yorkie activates transcription by recruiting the histone deacetylase HDAC1 and promoting histone deacetylation.

Authors:
W. Ge 1,2,4 ; F. Wang 1,2 ; Z. Nan 1,2 ; Z. Wang 1,2 ; J. Zhang 3 ; P. Guo 1,2 ; J. Lv 1,2 ; X. Xu 1,2 ; L. Wu 1,2 ; T. Guo 1,2 ; Q. Deng 1,2 ; Q. Zhou 3 ; X. Yang 1,2,4 ; Y. Xi 1,2,4


Institutes
1) Institute of Genetics, Zhejiang University School of Medicine, Zhejiang University, Hangzhou, China 310058; 2) College of Life Sciences, Zhejiang University, Hangzhou, China 310058; 3) Life Sciences Institute, Zhejiang University, Hangzhou, China 310058; 4) Department of Genetics, Zhejiang University School of Medicine, Zhejiang University, Hangzhou, China 310058.


Keyword: tissue growth

Abstract:

Control of organ size is a fundamental aspect in biology and plays important roles in development. The Hippo pathway is a conserved signaling cascade that controls tissue and organ size through the regulation of cell proliferation and apoptosis. Here, we report on the roles of Drosophila histone deacetylase HDAC1 in regulating the Hippo signaling pathway. Loss of HDAC1 function causes tissue undergrowth and the downregulation of Hippo target gene expression. Furthermore, Hippo pathway-mediated overgrowth and target gene expression are dependent on HDAC1. Mechanistically, we show that HDAC1 associates with the transcriptional coactivator Yorkie (Yki), and they co-occupy sites on chromatin at Hippo target gene loci. Finally, we provide evidence that Yki recruits HDAC1 to promote histone H3 lysine 27 (H3K27) deacetylation at Hippo target genes. Taken together, our findings suggest that recruiting of the histone deacetylase HDAC1 to Hippo target genes by Yki is required to activate gene expression, and highlight a positive role for HDAC1 in controlling specific gene expression program.