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Intellectual disability‐associated dBRWD 3 regulates gene expression through inhibition of HIRA / YEM ‐mediated chromatin deposition of histone H3.3
Author(s) -
Chen WeiYu,
Shih HsuehTzu,
Liu KueiYan,
Shih ZongSiou,
Chen LiKai,
Tsai TsungHan,
Chen MeiJu,
Liu Hsuan,
Tan Bertrand ChinMing,
Chen ChienYu,
Lee HsiuHsiang,
Loppin Benjamin,
AïtAhmed Ounissa,
Wu JuneTai
Publication year - 2015
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.15252/embr.201439092
Subject(s) - traditional chinese medicine , library science , histone h3 , histone , medicine , traditional medicine , gene , biology , genetics , alternative medicine , pathology , computer science
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 dBRWD3 , the Drosophila ortholog of the intellectual disability gene BRWD3 , regulates gene expression through H3.3, HIRA , and its associated chaperone Yemanuclein ( YEM ), the fly ortholog of mammalian Ubinuclein1. In dBRWD3 mutants, increased H3.3 levels disrupt gene expression, dendritic morphogenesis, and sensory organ differentiation. Inactivation of yem or H3.3 remarkably suppresses the global transcriptome changes and various developmental defects caused by dBRWD3 mutations. Our work thus establishes a previously unknown negative regulation of H3.3 and advances our understanding of BRWD 3‐dependent intellectual disability.