Premium
The unfolded protein response represses differentiation through the RPD3‐SIN3 histone deacetylase
Author(s) -
Schröder Martin,
Clark Robert,
Liu Chuan Yin,
Kaufman Randal J
Publication year - 2004
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/sj.emboj.7600233
Subject(s) - histone deacetylase , histone deacetylase 5 , microbiology and biotechnology , chromatin immunoprecipitation , rna splicing , promoter , biology , histone deacetylase 2 , hdac11 , unfolded protein response , endoplasmic reticulum , saccharomyces cerevisiae , histone , gene , genetics , gene expression , rna
In Saccharomyces cerevisiae , splicing of HAC1 mRNA is initiated in response to the accumulation of unfolded proteins in the endoplasmic reticulum by the transmembrane kinase‐endoribonuclease Ire1p. Spliced Hac1p (Hac1 i p) is a negative regulator of differentiation responses to nitrogen starvation, pseudohyphal growth, and meiosis. Here we show that the RPD3‐SIN3 histone deacetylase complex (HDAC), its catalytic activity, recruitment of the HDAC to the promoters of early meiotic genes ( EMG s) by Ume6p, and the Ume6p DNA‐binding site URS1 in the promoters of EMG s are required for nitrogen‐mediated negative regulation of EMG s and meiosis by Hac1 i p. Co‐immunoprecipitation experiments demonstrated that Hac1 i p can interact with the HDAC in vivo . Systematic analysis of double deletion strains revealed that HAC1 is a peripheral component of the HDAC. In summary, nitrogen‐induced synthesis of Hac1 i p and association of Hac1 i p with the HDAC are physiological events in the regulation of EMG s by nutrients. These data also define for the first time a gene class that is under negative control by the UPR, and provide the framework for a novel mechanism through which bZIP proteins repress transcription.