RRC ID 33239
著者 Chen WY, Shih HT, Liu KY, Shih ZS, Chen LK, Tsai TH, Chen MJ, Liu H, Tan BC, Chen CY, Lee HH, Loppin B, Aït-Ahmed O, Wu JT.
タイトル Intellectual disability-associated dBRWD3 regulates gene expression through inhibition of HIRA/YEM-mediated chromatin deposition of histone H3.3.
ジャーナル EMBO Rep
Abstract 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 BRWD3-dependent intellectual disability.
巻・号 16(4)
ページ 528-38
公開日 2015-4-1
DOI 10.15252/embr.201439092
PII embr.201439092
PMID 25666827
PMC PMC4388619
MeSH Animals Cell Cycle Proteins / genetics* Cell Cycle Proteins / metabolism Chromatin / chemistry Chromatin / metabolism DNA-Binding Proteins / antagonists & inhibitors DNA-Binding Proteins / genetics* DNA-Binding Proteins / metabolism Drosophila Proteins / antagonists & inhibitors Drosophila Proteins / genetics* Drosophila Proteins / metabolism Drosophila melanogaster / genetics* Drosophila melanogaster / growth & development Drosophila melanogaster / metabolism Gene Expression Regulation, Developmental* Histone Chaperones / genetics* Histone Chaperones / metabolism Histones / antagonists & inhibitors Histones / genetics* Histones / metabolism Humans Intellectual Disability / genetics Intellectual Disability / metabolism Intellectual Disability / pathology Morphogenesis / genetics Nuclear Proteins / antagonists & inhibitors Nuclear Proteins / genetics* Nuclear Proteins / metabolism RNA, Small Interfering / genetics RNA, Small Interfering / metabolism Sequence Homology, Amino Acid Signal Transduction Transcription Factors / genetics* Transcription Factors / metabolism
IF 7.497
引用数 8
WOS 分野 BIOCHEMISTRY & MOLECULAR BIOLOGY CELL BIOLOGY
リソース情報
ショウジョウバエ 12153R-1