A hupA mutation affected the production of cell surface structures in strains lacking a cysH gene [30] Based on proteomic studies, it was determined that the activities of nucleoid-associated proteins (NAPs) such as H-NS, HU, IHF, and FIS are also modulated by posttranslational modifications (PTMs) that signal differences in growth conditions; because none of the NAPs is known to bind any signaling ligands, these growth condition signals may be compensated for by these PTMs [31] DNA regulated by the NAPs (HU and Fis) directly or indirectly contributes to the symmetrical wave pattern of the base-pair substitution (BPS) rate [32] HU belongs to a family of DNA architectural proteins and acts mostly as a regulatory or accessory factor, stabilizing a correct nucleoprotein complex [33, 34, 35] For example, HU introduces negative supercoiling in covalently closed circular DNA in the presence of topoisomerase I [36, 37] Negative supercoiling induces significant looping under any appreciable tension [38] The HU protein has been shown to be involved in DNA replication [39, 40, 41]and the formation of transcription foci [42] and it modulates the binding of IHF to oriC [43]and stabilizes the DnaA oligomer bound to oriC [44] As another example, HU is required for the expression of σ^S factors [45] Recently, Oberto et al. showed that HU also plays an important role in the regulation of many genes in response to environmental changes and adaptation to stress, including changes in osmolarity, acid stress, SOS induction, and anaerobiosis [13, 46] HU remodels nucleoids during cell growth and environmental adaptation by promoting the formation of a condensed core surrounded by less-condensed isolated domains. It serves as a general microbial mechanism for transcriptional regulation to synchronize genetic responses during the cell cycle and to adapt to changing environments. [47] The negative supercoiling of DNA in Fis, H-NS, and HU transcription factors modulates their 3D shape and determines their molecular dynamics [48] The circular supercoiled DNA dynamically folds in particular higher-order structures (hyperplectonemes) [48] HU binds DNA without sequence specificity and with low affinity, but at low concentrations HU induces bends and at high concentrations HU induces the formation of rigid filaments [9, 19, 49, 50, 51]. The binding of this protein is destabilized when the tension of the double helix increases [52] Relationships between HU/IHF sequence, DNA-binding properties, and other protein features were identified based on sequence comparisons of thousands of known histone-like proteins from diverse bacterial phyla, in addition to a comparative modeling that demonstrated that HU protein 3D folding is even more conservative than the HU sequence [53] The effects of HU protein enhancements on DNA flexibility and the cyclization rate have been determined, based on a Monte Carlo approach, by Czapla et al. [54] Based on studies of single-molecule tracking, it was determined that on average at any time, 23% of HU molecules are in long-lived DNA-bound complexes at target sites, 77% are transiently, nonspecifically DNA-bound, and only 0.4% are in free diffusion between DNA strands; a diffusion coefficient of 0.33 μm²s^-1 was calculated [55]. The HU sliding is largely regulated by DNA bending dynamics [56] Based on the modified Pearson correlation coefficient (MPCC), a significant positive correlation between the RNAP and HU experimental distributions is robust [57] The Hu-α subunit plays significant and positive roles in promoting mixing and relaxation of the chromosome [58] The expression of hupA decreased in an rstA mutant and influenced the replication. RstA might affect initiation of replication through regulating the expression of the α-subunit of HU [59] Review: [60]