Open AccessdBRWD3 Regulates Tissue Overgrowth and Ectopic Gene Expression Caused by Polycomb Group Mutations
Author(s) -
HsuehTzu Shih,
Wei-Yu Chen,
Kwei-Yan Liu,
ZongSiou Shih,
Yi-Jyun Chen,
Paul-Chen Hsieh,
Kuan-Lin Kuo,
Kuo-How Huang,
PangHung Hsu,
Yawen Liu,
Shih-Peng Chan,
HsiuHsiang Lee,
Yu-Chen Tsai,
JuneTai Wu
Publication year - 2016
Publication title -
plos genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.587
H-Index - 233
eISSN - 1553-7404
pISSN - 1553-7390
DOI - 10.1371/journal.pgen.1006262
Subject(s) - ectopic expression , biology , polycomb group proteins , regulation of gene expression , gene , gene expression , mutant , chromatin , mutation , cell fate determination , histone , genetics , microbiology and biotechnology , cancer research , repressor , transcription factor
To maintain a particular cell fate, a unique set of genes should be expressed while another set is repressed. One way to repress gene expression is through Polycomb group (PcG) proteins that compact chromatin into a silent configuration. In addition to cell fate maintenance, PcG proteins also maintain normal cell physiology, for example cell cycle. In the absence of PcG, ectopic activation of the PcG-repressed genes leads to developmental defects and malignant tumors. Little is known about the molecular nature of ectopic gene expression; especially what differentiates expression of a given gene in the orthotopic tissue (orthotopic expression) and the ectopic expression of the same gene due to PcG mutations. Here we present that ectopic gene expression in PcG mutant cells specifically requires dBRWD3, a negative regulator of HIRA/Yemanuclein (YEM)-mediated histone variant H3.3 deposition. dBRWD3 mutations suppress both the ectopic gene expression and aberrant tissue overgrowth in PcG mutants through a YEM-dependent mechanism. Our findings identified dBRWD3 as a critical regulator that is uniquely required for ectopic gene expression and aberrant tissue overgrowth caused by PcG mutations.