dBRWD3 Regulates Tissue Overgrowth and Ectopic Gene Expression Caused by Polycomb Group Mutations.

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 mainta...

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Main Authors: Hsueh-Tzu Shih, Wei-Yu Chen, Kwei-Yan Liu, Zong-Siou Shih, Yi-Jyun Chen, Paul-Chen Hsieh, Kuan-Lin Kuo, Kuo-How Huang, Pang-Hung Hsu, Ya-Wen Liu, Shih-Peng Chan, Hsiu-Hsiang Lee, Yu-Chen Tsai, June-Tai Wu
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2016-09-01
Series:PLoS Genetics
Online Access:http://europepmc.org/articles/PMC5010193?pdf=render
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author Hsueh-Tzu Shih
Wei-Yu Chen
Kwei-Yan Liu
Zong-Siou Shih
Yi-Jyun Chen
Paul-Chen Hsieh
Kuan-Lin Kuo
Kuo-How Huang
Pang-Hung Hsu
Ya-Wen Liu
Shih-Peng Chan
Hsiu-Hsiang Lee
Yu-Chen Tsai
June-Tai Wu
author_facet Hsueh-Tzu Shih
Wei-Yu Chen
Kwei-Yan Liu
Zong-Siou Shih
Yi-Jyun Chen
Paul-Chen Hsieh
Kuan-Lin Kuo
Kuo-How Huang
Pang-Hung Hsu
Ya-Wen Liu
Shih-Peng Chan
Hsiu-Hsiang Lee
Yu-Chen Tsai
June-Tai Wu
author_sort Hsueh-Tzu Shih
collection DOAJ
description 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.
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spelling doaj.art-5ec658267b334fec96fda5242c7de4342022-12-22T03:00:29ZengPublic Library of Science (PLoS)PLoS Genetics1553-73901553-74042016-09-01129e100626210.1371/journal.pgen.1006262dBRWD3 Regulates Tissue Overgrowth and Ectopic Gene Expression Caused by Polycomb Group Mutations.Hsueh-Tzu ShihWei-Yu ChenKwei-Yan LiuZong-Siou ShihYi-Jyun ChenPaul-Chen HsiehKuan-Lin KuoKuo-How HuangPang-Hung HsuYa-Wen LiuShih-Peng ChanHsiu-Hsiang LeeYu-Chen TsaiJune-Tai WuTo 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.http://europepmc.org/articles/PMC5010193?pdf=render
spellingShingle Hsueh-Tzu Shih
Wei-Yu Chen
Kwei-Yan Liu
Zong-Siou Shih
Yi-Jyun Chen
Paul-Chen Hsieh
Kuan-Lin Kuo
Kuo-How Huang
Pang-Hung Hsu
Ya-Wen Liu
Shih-Peng Chan
Hsiu-Hsiang Lee
Yu-Chen Tsai
June-Tai Wu
dBRWD3 Regulates Tissue Overgrowth and Ectopic Gene Expression Caused by Polycomb Group Mutations.
PLoS Genetics
title dBRWD3 Regulates Tissue Overgrowth and Ectopic Gene Expression Caused by Polycomb Group Mutations.
title_full dBRWD3 Regulates Tissue Overgrowth and Ectopic Gene Expression Caused by Polycomb Group Mutations.
title_fullStr dBRWD3 Regulates Tissue Overgrowth and Ectopic Gene Expression Caused by Polycomb Group Mutations.
title_full_unstemmed dBRWD3 Regulates Tissue Overgrowth and Ectopic Gene Expression Caused by Polycomb Group Mutations.
title_short dBRWD3 Regulates Tissue Overgrowth and Ectopic Gene Expression Caused by Polycomb Group Mutations.
title_sort dbrwd3 regulates tissue overgrowth and ectopic gene expression caused by polycomb group mutations
url http://europepmc.org/articles/PMC5010193?pdf=render
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