The HU Regulon Is Composed of Genes Responding to Anaerobiosis, Acid Stress, High Osmolarity and SOS Induction

BackgroundThe Escherichia coli heterodimeric HU protein is a small DNA-bending protein associated with the bacterial nucleoid. It can introduce negative supercoils into closed circular DNA in the presence of topoisomerase I. Cells lacking HU grow very poorly and display many phenotypes.Methodology/Principal FindingsWe analyzed the transcription profile of every Escherichia coli gene in the absence of one or both HU subunits. This genome-wide in silico transcriptomic approach, performed in parallel with in vivo genetic experimentation, defined the HU regulon. This large regulon, which comprises 8% of the genome, is composed of four biologically relevant gene classes whose regulation responds to anaerobiosis, acid stress, high osmolarity, and SOS induction.Conclusions/SignificanceThe regulation a large number of genes encoding enzymes involved in energy metabolism and catabolism pathways by HU explains the highly pleiotropic phenotype of HU-deficient cells. The uniform chromosomal distribution of the many operons regulated by HU strongly suggests that the transcriptional and nucleoid architectural functions of HU constitute two aspects of a unique protein-DNA interaction mechanism.

背景 大肠杆菌（Escherichia coli）异二聚体HU蛋白是一类小型DNA弯曲蛋白，定位于细菌类核中。在拓扑异构酶I（topoisomerase I）存在时，该蛋白可向闭合环状DNA中引入负超螺旋。缺失HU蛋白的大肠杆菌细胞生长状况极差，并表现出多种表型。
材料与方法/主要结果 我们分析了单个或同时缺失HU亚基时，大肠杆菌所有基因的转录谱。本研究结合全基因组in silico转录组学方法与体内遗传实验，明确了HU调控子（regulon）的构成。该调控子涵盖基因组的8%，包含四类生物学功能相关的基因类别，其表达调控分别响应厌氧环境、酸胁迫、高渗胁迫与SOS诱导（SOS induction）。
结论与意义 HU蛋白调控大量参与能量代谢与分解代谢通路的酶编码基因，这一现象解释了HU缺失细胞所呈现的高度多效性表型。受HU调控的众多操纵子（operon）在染色体上的均匀分布，强烈提示HU的转录调控功能与类核结构功能，共同构成了一套独特的蛋白质-DNA相互作用机制的两个方面。