
@article {157490,
	title = {The Evolution of Sequence Specificity in a DNA Binding Protein Family.},
	journal = {J Mol Biol},
	volume = {437},
	year = {2025},
	month = {2025 Jul 15},
	pages = {169177},
	abstract = {<p>Transcriptional regulation enables bacteria to adjust to its environment. This is driven by transcription factors (TFs), which display DNA site recognition specificity with some flexibility built in. TFs, however, are not considered essential to a minimal cellular life. How did they evolve? It has been hypothesized that TFs evolve by gaining specificity (and other functions) on a background of non-specific chromosome structuring proteins. We used the IHF/HU family of DNA binding proteins, in which IHF binds DNA in a sequence-specific manner, whereas HU binds more indiscriminately, to test this hypothesis. We show that HUβ has been present from the bacterial root, while both IHF subunits emerged much later and diversified in Proteobacteria, with HUα having possibly arisen from transfer events in Gammaproteobacteria. By reconstructing ancestral sequences in-silico on a rooted phylogeny of IHF/HU we show that the common ancestor of this family was probably HU-like and therefore non-specific in binding DNA. IHF evolved from a branch of HU after HU had substantially diverged. Various residues characteristic of IHFα and shown to be involved in specific sequence recognition (at least in E. coli) have likely been co-opted from preexisting residues in HU, while those residues of IHFβ have likely evolved independently, suggesting that each of the IHF subunits has undergone different trajectories to acquire their DNA binding properties.</p>
},
	keywords = {HU; IHF; bacteria; evolution; transcription factor.},
	issn = {1089-8638},
	doi = {10.1016/j.jmb.2025.169177},
	url = {https://www.sciencedirect.com/science/article/pii/S0022283625002438?via\%3Dihub},
	author = {Nandy, Meghna and Krishnaswamy, Madhumitha and Sharda, Mohak and Seshasayee, Aswin Sai Narain}
}
@article {137347,
	title = {Cysteine desulfurase (IscS)-mediated fine-tuning of bioenergetics and SUF expression prevents  hypervirulence.},
	journal = {Sci Adv},
	volume = {9},
	year = {2023},
	month = {2023 Dec 15},
	pages = {eadh2858},
	abstract = {<p>Iron-sulfur (Fe-S) biogenesis requires multiprotein assembly systems, SUF and ISC, in most prokaryotes. () encodes a complete SUF system, the depletion of which was bactericidal. The ISC operon is truncated to a single gene (cysteine desulfurase), whose function remains uncertain. Here, we show that Δ is bioenergetically deficient and hypersensitive to oxidative stress, antibiotics, and hypoxia. Δ resisted killing by nitric oxide (NO). RNA sequencing indicates that IscS is important for expressing regulons of DosR and Fe-S-containing transcription factors, WhiB3 and SufR. Unlike wild-type , Δ could not enter a stable persistent state, continued replicating in mice, and showed hypervirulence. The operon was overexpressed in Δ during infection in a NO-dependent manner. Suppressing expression in Δ either by CRISPR interference or upon infection in inducible NO-deficient mice arrests hypervirulence. Together, redesigned the ISC system to "fine-tune" the expression of SUF machinery for establishing persistence without causing detrimental disease in the host.</p>
},
	keywords = {Animals, Energy Metabolism, Escherichia coli, Iron-Sulfur Proteins, Mice, Mycobacterium tuberculosis},
	issn = {2375-2548},
	doi = {10.1126/sciadv.adh2858},
	author = {Das, Mayashree and Sreedharan, Sreesa and Shee, Somnath and Malhotra, Nitish and Nandy, Meghna and Banerjee, Ushashi and Kohli, Sakshi and Rajmani, Raju S and Chandra, Nagasuma and Seshasayee, Aswin Sai Narain and Laxman, Sunil and Singh, Amit}
}
