Insight into the essential role of the Helicobacter pylori HP1043 orphan response regulator: Genome-wide identification and characterization of the DNA-binding sites

Many bacterial regulatory genes appear to be dispensable, as they can be deleted from the genome without loss of bacterial functionalities. In Helicobacter pylori, the hp1043 gene, also known as hsrA, is one of the transcriptional regulator that is essential for cell viability. This gene could not be deleted, nor the amount of protein modulated, supporting the hypothesis that HP1043 could be involved in the regulation of crucial cellular processes. Even though detailed structural data are available for the HP1043 protein, its targets are still ill-defined. Using Chromatin Immunoprecipitation-sequencing (ChIP-seq), one of the most powerful approaches to characterize protein-DNA interactions in vivo, we were able to identify genome-wide several new HP1043 binding sites. Moreover, in vitro DNA binding assays enabled precise mapping of the HP1043 binding sites on the new targets, revealing the presence of a conserved nucleotide sequence motif. Intriguingly, a significant fraction of the newly identified binding sites overlaps promoter regions controlling the expression of genes involved in translation. Accordingly, when protein translation was blocked, a significant induction of almost all HP1043 target genes was detected. These observations prompted us to propose HP1043 as a key regulator in H. pylori, likely involved in sensing and in coordinating the response to environmental conditions that provoke an arrest of protein synthesis. The essential role of HP1043 in coordinating central cellular processes is discussed.