Medical University of Vienna, Max F. Perutz Laboratories, Department of Medical Biochemistry, Campus Vienna Biocenter, Dr.-Bohr-Gasse 9/2, A-1030, Vienna, Austria.
Department of Systems Biology, Harvard Medical School, Boston, Massachusetts, 02115, USA.
Sci Rep. 2017 Aug 16;7(1):8308. doi: 10.1038/s41598-017-08239-9.
Morphological plasticity such as the yeast-to-hyphae transition is a key virulence factor of the human fungal pathogen Candida albicans. Hyphal formation is controlled by a multilayer regulatory network composed of environmental sensing, signaling, transcriptional modulators as well as chromatin modifications. Here, we demonstrate a novel role for the replication-independent HIR histone chaperone complex in fungal morphogenesis. HIR operates as a crucial modulator of hyphal development, since genetic ablation of the HIR complex subunit Hir1 decreases sensitivity to morphogenetic stimuli. Strikingly, HIR1-deficient cells display altered transcriptional amplitudes upon hyphal initiation, suggesting that Hir1 affects transcription by establishing transcriptional thresholds required for driving morphogenetic cell-fate decisions. Furthermore, ectopic expression of the transcription factor Ume6, which facilitates hyphal maintenance, rescues filamentation defects of hir1Δ/Δ cells, suggesting that Hir1 impacts the early phase of hyphal initiation. Hence, chromatin chaperone-mediated fine-tuning of transcription is crucial for driving morphogenetic conversions in the fungal pathogen C. albicans.
形态可塑性，如酵母到菌丝的转变，是人类真菌病原体白色念珠菌的关键毒力因子。菌丝形成受由环境感应、信号转导、转录调节剂以及染色质修饰组成的多层调节网络控制。在这里，我们证明了复制非依赖性 HIR 组蛋白伴侣复合物在真菌形态发生中的新作用。HIR 作为菌丝发育的关键调节剂发挥作用，因为 HIR 复合物亚基 Hir1 的遗传缺失降低了对形态发生刺激的敏感性。引人注目的是，HIR1 缺陷细胞在菌丝起始时表现出转录幅度的改变，这表明 Hir1 通过建立驱动形态发生细胞命运决定所需的转录阈值来影响转录。此外，转录因子 Ume6 的异位表达促进菌丝维持，可挽救 hir1Δ/Δ 细胞的丝状缺陷，表明 Hir1 影响菌丝起始的早期阶段。因此，染色质伴侣介导的转录精细调节对于驱动真菌病原体白色念珠菌的形态发生转换至关重要。
