Klopf Eva, Schmidt Heiko A, Clauder-Münster Sandra, Steinmetz Lars M, Schüller Christoph
Department of Applied Genetics and Cell Biology (DAGZ), University of Natural Resources and Life Sciences, Vienna (BOKU), UFT-Campus Tulln, Konrad Lorenz Strasse 24, 3430 Tulln, Austria.
Center for Integrative Bioinformatics Vienna (CIBIV), Max F. Perutz Laboratories, Medical University of Vienna, University of Vienna, Campus Vienna Biocenter 5 (VBC5), 1030 Vienna, Austria.
Nucleic Acids Res. 2017 Apr 20;45(7):3752-3766. doi: 10.1093/nar/gkw1292.
The conserved INO80 chromatin remodeling complex is involved in regulation of DNA damage repair, replication and transcription. It is commonly recruited to the transcription start region and contributes to the establishment of promoter-proximal nucleosomes. We find a substantial influence of INO80 on nucleosome dynamics and gene expression during stress induced transcription. Transcription induced by osmotic stress leads to genome-wide remodeling of promoter proximal nucleosomes. INO80 function is required for timely return of evicted nucleosomes to the 5΄ end of induced genes. Reduced INO80 function in Arp8-deficient cells leads to correlated prolonged transcription and nucleosome eviction. INO80 and the related complex SWR1 regulate incorporation of the H2A.Z isoform at promoter proximal nucleosomes. However, H2A.Z seems not to influence osmotic stress induced gene regulation. Furthermore, we show that high rates of transcription promote INO80 recruitment to promoter regions, suggesting a connection between active transcription and promoter proximal nucleosome remodeling. In addition, we find that absence of INO80 enhances bidirectional promoter activity at highly induced genes and expression of a number of stress induced transcripts. We suggest that INO80 has a direct repressive role via promoter proximal nucleosome remodeling to limit high levels of transcription in yeast.
保守的INO80染色质重塑复合物参与DNA损伤修复、复制和转录的调控。它通常被招募到转录起始区域，并有助于启动子近端核小体的形成。我们发现INO80在应激诱导转录过程中对核小体动力学和基因表达有重大影响。渗透应激诱导的转录导致启动子近端核小体在全基因组范围内重塑。INO80功能是被驱逐的核小体及时返回诱导基因5΄端所必需的。Arp8缺陷细胞中INO80功能降低导致转录和核小体驱逐相关延长。INO80和相关复合物SWR1调节H2A.Z亚型在启动子近端核小体中的掺入。然而，H2A.Z似乎不影响渗透应激诱导的基因调控。此外，我们表明高转录速率促进INO80招募到启动子区域，表明活跃转录与启动子近端核小体重塑之间存在联系。此外，我们发现INO80缺失增强了高诱导基因的双向启动子活性以及一些应激诱导转录本的表达。我们认为INO80通过启动子近端核小体重塑具有直接的抑制作用，以限制酵母中的高水平转录。
