title: dBRWD3 Regulates Tissue Overgrowth and Ectopic Gene Expression Caused by Polycomb Group Mutations.
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.
authors: Institute of Molecular Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan.
authors: Hsueh-Tzu
authors: HT
authors: Shih
authors: Institute of Molecular Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan.
authors: Wei-Yu
authors: WY
authors: Chen
authors: Institute of Molecular Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan.
authors: Kwei-Yan
authors: KY
authors: Liu
authors: Institute of Molecular Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan.
authors: Zong-Siou
authors: ZS
authors: Shih
authors: Institute of Molecular Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan.
authors: Yi-Jyun
authors: YJ
authors: Chen
authors: Department of Anatomical Pathology, Far Eastern Memorial Hospital, New Taipei City, Taiwan.
authors: Paul-Chen
authors: PC
authors: Hsieh
authors: Graduate Institute of Toxicology, National Taiwan University College of Medicine, Taipei, Taiwan.|Department of Urology, National Taiwan University College of Medicine and Hospital, Taipei, Taiwan.
authors: Kuan-Lin
authors: KL
authors: Kuo
authors: Department of Urology, National Taiwan University College of Medicine and Hospital, Taipei, Taiwan.
authors: Kuo-How
authors: KH
authors: Huang
authors: Department of Bioscience and Biotechnology, National Taiwan Ocean University, Keelung, Taiwan.
authors: Pang-Hung
authors: PH
authors: Hsu
authors: Institute of Molecular Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan.
authors: Ya-Wen
authors: YW
authors: Liu
authors: Graduate Institute of Microbiology, College of Medicine, National Taiwan University, Taipei, Taiwan.|Genome and Systems Biology Degree Program, College of Life Science, National Taiwan University, Taipei, Taiwan.
authors: Shih-Peng
authors: 0000-0001-6322-2821
authors: SP
authors: Chan
authors: Institute of Molecular Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan.
authors: Hsiu-Hsiang
authors: 0000-0001-7707-8461
authors: HH
authors: Lee
authors: Department of Life Science and Life Science Center, Tunghai University, Taichung, Taiwan.
authors: Yu-Chen
authors: YC
authors: Tsai
authors: Institute of Molecular Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan.
authors: June-Tai
authors: JT
authors: Wu
mesh_terms: D000818:Animals; D002453:Cell Cycle / Q000235:genetics*; D018797:Cell Cycle Proteins / Q000096:biosynthesis / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics*; D002843:Chromatin / Q000235:genetics; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics; D029721:Drosophila Proteins / Q000096:biosynthesis / Q000235:genetics*; D004331:Drosophila melanogaster / Q000235:genetics / Q000254:growth & development; D005123:Eye / Q000254:growth & development / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D056488:Histone Chaperones / Q000096:biosynthesis / Q000235:genetics; D006657:Histones / Q000235:genetics; D060227:Imaginal Discs / Q000254:growth & development / Q000378:metabolism; D009154:Mutation; D009687:Nuclear Proteins / Q000096:biosynthesis / Q000235:genetics; D063146:Polycomb-Group Proteins / Q000096:biosynthesis / Q000235:genetics*; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics*
chemical_list: C524125:BRWD3 protein, Drosophila; D018797:Cell Cycle Proteins; D002843:Chromatin; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; C488124:Hira protein, Drosophila; D056488:Histone Chaperones; D006657:Histones; D009687:Nuclear Proteins; D063146:Polycomb-Group Proteins; D014157:Transcription Factors; C075160:yem protein, Drosophila