Redox-dependent Condensation of the Mycobacterial Nucleoid by WhiB4

Publication date: Available online 13 August 2018Source: Redox BiologyAuthor(s): Manbeena Chawla, Saurabh Mishra, Kushi Anand, Pankti Parikh, Mansi Mehta, Manika Vij, Taru Verm, Parul Singh, Kishor Jakkala, H N Verma, Parthasarathi AjitKumar, Munia Ganguli, Aswin Sai Narain Seshasayee, Amit SinghAbstractOxidative stress response in bacteria is mediated through coordination between the regulators of oxidant-remediation systems (e.g. OxyR, SoxR) and nucleoid condensation (e.g. Dps, Fis). However, these genetic factors are either absent or rendered non-functional in the human pathogen Mycobacterium tuberculosis (Mtb). Therefore, how Mtb organizes genome architecture and regulates gene expression to counterbalance oxidative imbalance is unknown. Here, we report that an intracellular redox-sensor, WhiB4, dynamically links genome condensation and oxidative stress response in Mtb. Disruption of WhiB4 affects the expression of genes involved in maintaining redox homeostasis, central metabolism, and respiration under oxidative stress. Notably, disulfide-linked oligomerization of WhiB4 in response to oxidative stress activates the protein’s ability to condense DNA. Further, overexpression of WhiB4 led to hypercondensation of nucleoids, redox imbalance and increased susceptibility to oxidative stress, whereas WhiB4 disruption reversed this effect. In accordance with the findings in vitro, ChIP-Seq data demonstrated non-specific binding of WhiB4 to GC-rich regions of the Mtb genome. La...

Source: Redox Biology - August 13, 2018 Category: Biology Source Type: research