Growth-Phase-Specific Modulation of Cell Morphology and Gene Expression by an Archaeal Histone Protein.
Growth-Phase-Specific Modulation of Cell Morphology and Gene Expression by an Archaeal Histone Protein.
复制标题
古细胞组蛋白对细胞形态和基因表达的生长期特异性调节。
DOI：
10.1128/mbio.00649-15
复制
发表时间：
2015-09-08
期刊：
影响因子：
6.4
通讯作者：
Schmid AK
中科院分区：
文献类型：
--
作者：
Dulmage KA;Todor H;Schmid AK
在生命的所有三个领域中，生物体使用非特异性DNA结合蛋白来压缩和组织基因组，以及在全球范围内调节转录。组蛋白是真核生物的主要核蛋白，其进化起源可以追溯到古生菌。然而，并不是所有的古细菌都使用这种蛋白质作为主要的DNA包装成分，这就提出了关于组蛋白在古细菌染色质功能中的作用的问题。在这里，定量表型，转录组学和蛋白质组学测定进行缺失和过度表达突变体的唯一的组蛋白蛋白的超盐碱适应盐古菌模式生物盐杆菌salinarum。该蛋白在所有测序的盐古菌物种中高度保守，并保持真核组蛋白功能所需的标志残基。令人惊讶的是，尽管在序列水平上存在这种保守性，但与其他古生菌或真核生物不同，盐生海鞘组蛋白是调节细胞形状所必需的，但不是生存所必需的。组蛋白缺失菌株的全基因组表达变化是全局性的，显著的，但在倍数变化、双向性和生长期依赖性方面是微妙的。从染色质富集蛋白质的质谱蛋白质组学鉴定产生的组蛋白和推定的核苷酸相关蛋白的水平类似于那些转录因子，与开放和转录活性基因组一致。综上所述，这些数据表明，组蛋白在盐藻DNA压缩中起次要作用，但在生长期依赖的基因表达和细胞形状调节中起重要作用。盐古菌中组蛋白的功能更类似于基因表达的调节因子，而不是像典型的真核组蛋白那样的染色质组织蛋白。组蛋白是真核生物染色质的主要蛋白质组分，是基因组包装和表达调控所必需的。目前的范式认为，基因编码组蛋白的古生菌也使用这些蛋白质来包装DNA。相比之下，在这里，我们表明，唯一的组蛋白编码的基因组中的盐适应性古菌盐杆菌的盐是不必要的，不太可能参与DNA压缩，尽管保守的残基重要的真核组蛋白。相反，H.salinarum组蛋白是基因表达和细胞形状的全局调节所必需的。这些数据与以下假设一致：在所有其他已知的盐适应古菌中高度保守的盐生菌组蛋白在基因调控和细胞形状维持中起着新的作用。鉴于古生菌具有真核组蛋白的祖先形式，这项研究对于理解组蛋白功能的进化具有重要意义。
In all three domains of life, organisms use nonspecific DNA-binding proteins to compact and organize the genome as well as to regulate transcription on a global scale. Histone is the primary eukaryotic nucleoprotein, and its evolutionary roots can be traced to the archaea. However, not all archaea use this protein as the primary DNA-packaging component, raising questions regarding the role of histones in archaeal chromatin function. Here, quantitative phenotyping, transcriptomic, and proteomic assays were performed on deletion and overexpression mutants of the sole histone protein of the hypersaline-adapted haloarchaeal model organism Halobacterium salinarum. This protein is highly conserved among all sequenced haloarchaeal species and maintains hallmark residues required for eukaryotic histone functions. Surprisingly, despite this conservation at the sequence level, unlike in other archaea or eukaryotes, H. salinarum histone is required to regulate cell shape but is not necessary for survival. Genome-wide expression changes in histone deletion strains were global, significant but subtle in terms of fold change, bidirectional, and growth phase dependent. Mass spectrometric proteomic identification of proteins from chromatin enrichments yielded levels of histone and putative nucleoid-associated proteins similar to those of transcription factors, consistent with an open and transcriptionally active genome. Taken together, these data suggest that histone in H. salinarum plays a minor role in DNA compaction but important roles in growth-phase-dependent gene expression and regulation of cell shape. Histone function in haloarchaea more closely resembles a regulator of gene expression than a chromatin-organizing protein like canonical eukaryotic histone. Histones comprise the major protein component of eukaryotic chromatin and are required for both genome packaging and global regulation of expression. The current paradigm maintains that archaea whose genes encode histone also use these proteins to package DNA. In contrast, here we demonstrate that the sole histone encoded in the genome of the salt-adapted archaeon Halobacterium salinarum is both unessential and unlikely to be involved in DNA compaction despite conservation of residues important for eukaryotic histones. Rather, H. salinarum histone is required for global regulation of gene expression and cell shape. These data are consistent with the hypothesis that H. salinarum histone, strongly conserved across all other known salt-adapted archaea, serves a novel role in gene regulation and cell shape maintenance. Given that archaea possess the ancestral form of eukaryotic histone, this study has important implications for understanding the evolution of histone function.