1. dBRWD3 Regulates Tissue Overgrowth and Ectopic Gene Expression Caused by Polycomb Group Mutations.
- Author
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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, and Wu JT
- Subjects
- Animals, Cell Cycle Proteins biosynthesis, Cell Cycle Proteins genetics, Chromatin genetics, DNA-Binding Proteins biosynthesis, DNA-Binding Proteins genetics, Drosophila Proteins biosynthesis, 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, Transcription Factors biosynthesis, Cell Cycle genetics, Cell Differentiation genetics, Drosophila Proteins genetics, Polycomb-Group Proteins genetics, Transcription Factors genetics
- 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., Competing Interests: The authors have declared that no competing interests exist.
- Published
- 2016
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