Molecular dissection of Mycobacterium tuberculosis integration host factor reveals novel insights into the mode of DNA binding and nucleoid compaction.

Abstract

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H‐NS, IHF, and DnaA lead to changes in nucleoid organizations, replication initiation, and cell division

“…In agreement with previous reports , we found that both the absence of H‐NS or the presence of extra H‐NS led to a dramatic increase in the number of cells with uncompacted nucleoids in a medium‐independent manner (Figure ). An increase in the number of cells with uncompacted nucleoids was also observed in the hns 206 mutant (Figure ), indicating that the availability of H‐NS and fully functional H‐NS is required for correct nucleoid compaction.…”

“…The 15.5 kDa H‐NS protein is believed to play an important role in nucleoid compaction and organization by bridging distant DNA segments . Also IHF, as a member of nucleoid‐associated proteins, promotes nucleoid compaction .…”

Analysis of nucleoid‐associated protein‐binding regions reveals DNA structural features influencing genome organization in Mycobacterium tuberculosis

“…S5) indicates a significantly higher curvature (values tending towards 0) compared with UR ( P ≤ 0.05) and DR ( P ≤ 0.0001). A relevant study reports wild‐type mIHF binds to curved DNA with higher affinity excluding the DNA‐binding variants [45]. Differences were also significant for MtHU–DNA‐binding centre region compared to the UR ( P ≤ 0.0001) and DR ( P ≤ 0.0001).…”

“…Co‐crystal structure analysis and high‐throughput studies on EspR and MtHU indicated that they are divulged to interact in a sequence‐specific way, recognizing conserved motifs in genomic context [38]. Whereas another member of the mycobacterial NAP family, that is mIHF, has been found to be non‐sequence‐specific, rather it was known to bind preferably at local DNA deformations such as curved DNA [45]. However, the sequence logo [77] for binding regions of (−50 to +50 position) six NAPs does not depict any specific enrichment of consensus sequences (Fig.…”

“…It has an affinity for binding to AT‐rich sequences in the mycobacterial genome and results in the DNA molecule bridge formation [41–43]. The mycobacterial integration host factor (mIHF) is a 20.81 kDa protein encoded by Rv1388 and exhibits DNA‐bending, bridging and wrapping properties [44,45]. MtHU ( Mycobacterium tuberculosis HU) is a small, 22.1 kDa basic protein involved in DNA bending [46].…”