Cooperation between the INO80 Complex and Histone Chaperones Determines Adaptation of Stress Gene Transcription in the Yeast Saccharomyces cerevisiae

Abstract

In yeast, environmental stresses provoke sudden and dramatic increases in gene expression at stressinducible loci. Stress gene transcription is accompanied by the transient eviction of histones from the promoter and the transcribed regions of these genes. We found that mutants defective in subunits of the INO80 complex, as well as in several histone chaperone systems, exhibit extended expression windows that can be correlated with a distinct delay in histone redeposition during adaptation. Surprisingly, Ino80 became associated with the ORFs of stress genes in a stress-specific way, suggesting a direct function in the repression during adaptation. This recruitment required elongation by RNA polymerase (Pol) II but none of the histone modifications that are usually associated with active transcription, such as H3 K4/K36 methylation. A mutant lacking the Asf1-associated H3K56 acetyltransferase Rtt109 or Asf1 itself also showed enhanced stress-induced transcript levels. Genetic data, however, suggest that Asf1 and Rtt109 function in parallel with INO80 to restore histone homeostasis, whereas Spt6 seems to have a function that overlaps that of the chromatin remodeler. Thus, chromatin remodeling by INO80 in cooperation with Spt6 determines the shape of the expression profile under acute stress conditions, possibly by an elongation-dependent mechanism.Local chromatin structures are decisive for the correct interpretation of genetic information (reviewed in reference 19). For example, positioned nucleosomes mark the beginnings and ends of transcription units. Transcription is one of the major cellular processes that require reversible restructuration of chromatin. RNA polymerase (Pol) function demands adjustments of the local chromatin structure of both promoter and entire transcribed regions (e.g., see references 23, 31, and 43). How RNA Pol II and associated factors cooperate in order to transiently displace nucleosomes is not yet fully understood (reviewed in reference 22). Saccharomyces cerevisiae cells exposed to changes in environmental conditions respond by rapidly changing the transcript levels of many genes. Under proper circumstances, these genes under environmental control are intensively and transiently transcribed (13) and thus cause chromatin rearrangements during both induction and adaptation. For example, heat stress causes reduced density of the local chromatin of heat stress-induced loci (45). Thus, one interesting feature of these loci is that promoter activation, chromatin clearance, and Pol recruitment happen at a rapid pace.Structural alterations of chromatin during transcription comprise covalent modifications of histones, replacement of canonical histones by variants, and ATP-dependent chromatin remodeling (reviewed in reference 55). During elongation, RNA Pol II attracts several histone-modifying activities required for the restoration of chromatin. One class consists of enzymes acting sequentially such as the Set2 histone methyltransferase and the Rpd3S histone deacetylase complex that also hel...

Threonine-4 of the budding yeast RNAP II CTD couples transcription with Htz1-mediated chromatin remodeling

“…In addition to roles in double-strand break repair and stalled replication fork recovery (51), INO80c is required for full induction of a number of genes, including reporter genes containing upstream activation sequences of the PHO5 or GAL1 promoters (52,53). INO80c associates with many RNAP II promoters and is recruited to genes when they are activated (54,55), including PHO5, where it was shown to be required for nucleosome remodeling and gene induction (52). In the absence of Ino80, Htz1 localization across the genome is perturbed, with increased occupancy at some loci and reduced occupancy at others, thereby linking INO80c with Htz1 dynamics (36).…”

Categorizing Biases in High-Confidence High-Throughput Protein-Protein Interaction Data Sets

“…6A shows the detailed complex-complex interaction mapping for the three high-confidence networks. The interaction data support the RNA polymerases II and III connection with chromatin remodeling modules, via RNA polymerases II interacting with the nucleosome remodeling complexes SWI/SNF and INO80 and via RNA polymerases III interacting with the chromatin structure remodeling (RSC) complex and nucleosomal protein complexes (histones) (41,42). DNA interacting assemblies, such as TAFIIs and RNA polymerase II mediator complex (SRB), were also directly linked via protein-protein interactions to RNA synthesis complexes, whereas others, such as, histone acetyltransferase complexes [SAGA (43) and NuA4 (44)] and histone deacetylase complex were indirectly linked (43)(44)(45)(46).…”

Preferential Repair of DNA Double-strand Break at the Active Gene in Vivo

“…In support of this hypothesis, a recent study (57) implicated the interaction of RNA polymerase II with RPA (replication protein A complex), which is involved in DSB repair. Further, the INO80 chromatin remodeling complex that promotes DSB repair is recruited to the gene in a transcription-dependent manner (58,59). Similarly, the recruitment of the MRX (Mre11p-Rad50p-Xrs2p) complex and Ku proteins to the DSB site might be promoted by RNA polymerase II or transcription machinery to stimulate DSB repair.…”