Mot1, Ino80C, and NC2 Function Coordinately to Regulate Pervasive Transcription in Yeast and Mammals

Abstract

Pervasive transcription initiates from cryptic promoters and is observed in eukaryotes ranging from yeast to mammals. The Set2-Rpd3 regulatory system prevents cryptic promoter function within expressed genes. However, conserved systems that control pervasive transcription within intergenic regions have not been well established. Here we show that Mot1, Ino80 chromatin remodeling complex (Ino80C), and NC2 colocalize on chromatin and coordinately suppress pervasive transcription in S. cerevisiae and murine embryonic stem cells (mESCs). In yeast, all three proteins bind subtelomeric heterochromatin through a Sir3-stimulated mechanism and to euchromatin via a TBP-stimulated mechanism. In mESCs, the proteins bind to active and poised TBP-bound promoters along with promoters of polycomb-silenced genes apparently lacking TBP. Depletion of Mot1, Ino80C or NC2 by anchor away in yeast or RNAi in mESCs leads to near-identical transcriptome phenotypes, with new subtelomeric transcription in yeast, and greatly increased pervasive transcription in both yeast and mESCs.

Conserved crosstalk between histone deacetylation and H3K79 methylation generates DOT1L‐dose dependency in HDAC1‐deficient thymic lymphoma

“…Our analysis shows that inactivation of the INO80 complex by deletion of ARP5 does not specifically affect H3K79 methylation at the promoters of genes that are also regulated by Rpd3, although INO80 might affect Rpd3 target genes somewhat more than non‐target genes (Fig EV2F). This finding is in agreement with the observation that INO80 affects the majority of genes in the yeast genomes (Xue et al , , ) whereas Rpd3 regulates H3K79 methylation at a smaller subset of genes. Finally, we examined the role of H2B ubiquitination in mediating the effect of Rpd3.…”

“…We also compared the changes in H3K79 methylation in mutants lacking Rpd3 with changes in H3K79 methylation in mutants lacking INO80 (Data ref: Xue et al , ). This chromatin remodeler has been shown to keep transcription and H3K79me3 at intergenic regions at bay (Xue et al , , ). Our analysis shows that inactivation of the INO80 complex by deletion of ARP5 does not specifically affect H3K79 methylation at the promoters of genes that are also regulated by Rpd3, although INO80 might affect Rpd3 target genes somewhat more than non‐target genes (Fig EV2F).…”

Greater genetic and regulatory plasticity of retained duplicates in Epichloë endophytic fungi

“…Under the hypothesis that retained duplicates have greater expression plasticity, duplicated genes might be expected to show higher diversity in their regulatory regions than single copy genes. The region immediately upstream of the coding sequence (1 kb) is rich in promoter elements in yeast (Dobi & Winston, ; Elion & Warner, ; Petrascheck et al, ; Xue et al, ) with similar patterns thought to hold for other fungi (Basse & Farfsing, ; Fischer, Durand, & Fevre, ). We thus examined the 1‐kb upstream regions of retained duplicates and single copy genes, and compared genetic distances between conspecific strains (Figure d).…”

The chromatin remodeling protein INO80 contributes to the removal of H2A.Z at the p53‐binding site of the p21 gene in response to doxorubicin

“…In yeast and murine embryonic stem cells, the INO80 complex can recruit to the TSS region and directly repress promoter-proximal nucleosome remodeling to limit transcription [33,34]. In yeast and murine embryonic stem cells, the INO80 complex can recruit to the TSS region and directly repress promoter-proximal nucleosome remodeling to limit transcription [33,34].…”

“…In normal conditions, the INO80 complex may directly inhibit p21 expression by repressing promoter-proximal nucleosome remodeling [33,34]. In normal conditions, the INO80 complex may directly inhibit p21 expression by repressing promoter-proximal nucleosome remodeling [33,34].…”