RRC ID 46761
著者 Shih HT, Chen WY, Liu KY, Shih ZS, Chen YJ, Hsieh PC, Kuo KL, Huang KH, Hsu PH, Liu YW, Chan SP, Lee HH, Tsai YC, Wu JT.
タイトル dBRWD3 Regulates Tissue Overgrowth and Ectopic Gene Expression Caused by Polycomb Group Mutations.
ジャーナル PLoS Genet
Abstract 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.
巻・号 12(9)
ページ e1006262
公開日 2016-9-1
DOI 10.1371/journal.pgen.1006262
PII PGENETICS-D-15-02868
PMID 27588417
PMC PMC5010193
MeSH Animals Cell Cycle / genetics* Cell Cycle Proteins / biosynthesis Cell Cycle Proteins / genetics Cell Differentiation / genetics* Chromatin / genetics DNA-Binding Proteins / biosynthesis DNA-Binding Proteins / genetics Drosophila Proteins / biosynthesis Drosophila Proteins / genetics* Drosophila melanogaster / genetics Drosophila melanogaster / growth & development Eye / growth & development Eye / metabolism Gene Expression Regulation, Developmental Histone Chaperones / biosynthesis Histone Chaperones / genetics Histones / genetics Imaginal Discs / growth & development Imaginal Discs / metabolism Mutation Nuclear Proteins / biosynthesis Nuclear Proteins / genetics Polycomb-Group Proteins / biosynthesis Polycomb-Group Proteins / genetics* Transcription Factors / biosynthesis Transcription Factors / genetics*
IF 5.175
引用数 1
WOS 分野 GENETICS & HEREDITY
リソース情報
ショウジョウバエ 3886R-4 18412R-1 6502R-3 32443R-1 7405R-1 3319R-1