Intellectual disability‐associated dBRWD3 regulates gene expression through inhibition of HIRA/YEM‐mediated chromatin deposition of histone H3.3. (9th February 2015)

• Record Type: Journal Article
• Authors: Chen, Wei‐Yu; Shih, Hsueh‐Tzu; Liu, Kuei‐Yan; Shih, Zong‐Siou; Chen, Li‐Kai; Tsai, Tsung‐Han; Chen, Mei‐Ju; Liu, Hsuan; Tan, Bertrand Chin‐Ming; Chen, Chien‐Yu; Lee, Hsiu‐Hsiang; Loppin, Benjamin; Aït‐Ahmed, Ounissa; Wu, June‐Tai
• Is Part Of: EMBO reports. Volume 16:Number 4(2015:Apr.)
• Page Start: 528
• Page End: 538
• Publication Date: 2015-02-09
• Subjects: Molecular biology -- Periodicals; Molecular Biology -- Periodicals; Molecular biology; Periodicals; 572.8
• DOI: 10.15252/embr.201439092
• Languages: English
• ISSNs: 1469-221X

Abstract

<abstract abstract-type="main" id="embr201439092-abs-0001"> <title>Abstract</title> <p>Many causal mutations of intellectual disability have been found in genes involved in epigenetic regulations. Replication‐independent deposition of the histone H3.3 variant by the HIRA complex is a prominent nucleosome replacement mechanism affecting gene transcription, especially in postmitotic neurons. However, how HIRA‐mediated H3.3 deposition is regulated in these cells remains unclear. Here, we report that <italic>dBRWD3</italic>, the <italic>Drosophila</italic> ortholog of the intellectual disability gene <italic>BRWD3</italic>, regulates gene expression through H3.3, HIRA, and its associated chaperone Yemanuclein (YEM), the fly ortholog of mammalian Ubinuclein1. In <italic>dBRWD3</italic> mutants, increased H3.3 levels disrupt gene expression, dendritic morphogenesis, and sensory organ differentiation. Inactivation of <italic>yem</italic> or <italic>H3.3</italic> remarkably suppresses the global transcriptome changes and various developmental defects caused by <italic>dBRWD3</italic> mutations. Our work thus establishes a previously unknown negative regulation of H3.3 and advances our understanding of BRWD3‐dependent intellectual disability.</p> </abstract>