4.6 Article

Increased histone acetylation is the signature of repressed state on the genes transcribed by RNA polymerase III

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GENE
卷 893, 期 -, 页码 -

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DOI: 10.1016/j.gene.2023.147958

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Acetylations; Gcn5; Pol III; Repression; Rpd3; SNR6; Transcription; U6 snRNA

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Covalent modifications, such as histone acetylations, are associated with transcriptionally active chromatin regions. Pol III-transcribed genes are repressed under stress conditions, and this repression is linked to increased histone acetylations. A nucleosome in the upstream region of the SNR6 gene plays a regulatory role during repression, with different dynamics of H3K9 and H3K14 acetylations. The increase in acetylations on this nucleosome may be part of the signaling mechanisms preparing cells for stress-related repression and reactivation.
Several covalent modifications are found associated with the transcriptionally active chromatin regions constituted by the genes transcribed by RNA polymerase (pol) II. Pol III-transcribed genes code for the small, stable RNA species, which participate in many cellular processes, essential for survival. Pol III transcription is repressed under most of the stress conditions by its negative regulator Maf1. We found that most of the histone acetylations increase with starvation-induced repression on several genes transcribed by the yeast pol III. On one of these genes, SNR6 (coding for the U6snRNA), a strongly positioned nucleosome in the gene upstream region plays regulatory role under repression. On this nucleosome, the changes in H3K9 and H3K14 acetylations show different dynamics. During repression, acetylation levels on H3K9 show steady increase whereas H3K14 acetylation increases with a peak at 40 min after which levels reduce. Both the levels settle by 2 hr to a level higher than the active state, which revert to normal levels with nutrient repletion. The increase in H3 acetylations is seen in the mutants reported to show reduced SNR6 transcription but not in the maf1 Delta cells. This increase on a regulatory nucleosome may be part of the signaling mechanisms, which prepare cells for the stress-related quick repression as well as reactivation. The contrasting association of the histone acetylations with pol II and pol III transcription may be an important consideration to make in research studies focused on drug developments targeting histone modifications.

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