Lee Min Kyung, Kang Byunghee, Shin Min-Kyung, Kim Yoon Ki, Kim Hye Young, Lee Soo Young, Roh Tae-Young, Kim TaeSoo
Department of Life Sciences and Multitasking Macrophage Research Center, Ewha Womans University, Seoul 03760, Republic of Korea.
Department of Life Sciences, Pohang University of Science and Technology (POSTECH), Pohang 37673, Republic of Korea.
Nucleic Acids Res. 2025 Apr 10;53(7). doi: 10.1093/nar/gkaf256.
In yeast, Hda1 histone deacetylase complex (Hda1C) plays an important role in transcriptional regulation by modulating histone acetylation. We here explored the changes in Hda1C binding in nutrient-rich and -starved conditions. Chromatin immunoprecipitation sequencing revealed that starvation alters RNA Pol II and Hda1C binding to coding genes in a highly correlated manner. Interestingly, we discovered RNA Pol II transcription-independent recruitment of Hda1C to intergenic regions, particularly the upstream regulatory sequences (URS) of ribosomal protein (RP) genes, which are enriched with Rap1 binding sites. Under nutrient starvation, Rap1 contributes to the recruitment of Hda1C to these URS regions, where Hda1C deacetylates histones, thereby fine-tuning basal gene expression and delaying RP gene reactivation. Furthermore, Hda1C is also required for RNA Pol I transcription of ribosomal RNAs (rRNAs) and RNA Pol III transcription of transfer RNA (tRNA) genes, especially in nutrient-limited conditions. Significantly, Hda1C mutants are sensitive to translation inhibitors and display altered ribosome profiles. Thus, Hda1C may coordinate transcriptional regulation within the nucleus with translation control in the cytoplasm and could be a key regulator of gene expression responses to nutrient stress.
在酵母中，Hda1组蛋白去乙酰化酶复合体（Hda1C）通过调节组蛋白乙酰化在转录调控中发挥重要作用。我们在此探究了营养丰富和饥饿条件下Hda1C结合的变化。染色质免疫沉淀测序显示，饥饿以高度相关的方式改变RNA聚合酶II（RNA Pol II）和Hda1C与编码基因的结合。有趣的是，我们发现RNA Pol II转录非依赖性地将Hda1C募集到基因间区域，特别是核糖体蛋白（RP）基因的上游调控序列（URS），这些区域富含Rap1结合位点。在营养饥饿条件下，Rap1有助于将Hda1C募集到这些URS区域，Hda1C在那里使组蛋白去乙酰化，从而微调基础基因表达并延迟RP基因的重新激活。此外，Hda1C对于核糖体RNA（rRNA）的RNA Pol I转录和转运RNA（tRNA）基因的RNA Pol III转录也是必需的，尤其是在营养受限的条件下。值得注意的是，Hda1C突变体对翻译抑制剂敏感并表现出改变的核糖体谱。因此，Hda1C可能在细胞核内协调转录调控与细胞质中的翻译控制，并且可能是基因表达对营养应激反应的关键调节因子。
