Biology subjects

Nago, N.

Publications and source records attributed to Nago, N..

3 recordsLinked to original sources

bioRxiv2026

Tunable kinetic destabilization governs RNA polymerase passage through a DNA-bound transcription factor

Eukaryotic transcription factors recognize short motifs, creating abundant binding sites within gene bodies and potential collisions with elongating RNA polymerases, yet how such encounters are resolved remains unclear. Here, we use optical tweezers to monitor RNA polymerase transcription through DNA-bound Egr-1, a zinc-finger transcription factor. Using DNA-fluctuation suppression as a readout of polymerase arrival, we show that Egr-1 delays elongation in an orientation- and rNTP-dependent manner, whereas force measurements indicate that RNAP does not bypass the TF by mechanical eviction. Instead, RNAP destabilizes the Egr-1-DNA complex over a short, structured interaction zone, increasing TF dissociation non-monotonically with distance. Monte Carlo simulations incorporating these kinetic changes recapitulate passage-time distributions. CpG methylation shortens Egr-1 residence time and largely eliminates the TF-dependent delay, suggesting a role for gene-body methylation in reducing kinetic barriers to elongation. These results reveal DNA-bound TFs as tunable barriers that locally shape transcription elongation.

biophysics↗

bioRxiv2025

Intrinsically disordered regions facilitate Msn2 target search to drive promoter selectivity

Transcription factors (TFs) regulate gene expression by binding specific DNA motifs, yet only a fraction of putative sites is occupied in vivo. Intrinsically disordered regions (IDRs) have emerged as key contributors to promoter selectivity, but the underlying mechanisms remain incompletely understood. Here, we use single-molecule optical tweezers to dissect how IDRs influence DNA binding by Msn2, a yeast stress-response regulator. We show that IDRs facilitate initial non-specific association with DNA and promote one-dimensional diffusion toward target motifs, supported by charge-mediated interactions. Remarkably, the IDR-dependent search mechanism displays sequence sensitivity, with promoter-derived sequences enhancing both initial binding and sliding rates, demonstrating that Msn2-DNA interactions alone are sufficient to confer promoter selectivity in the absence of chromatin or cofactors. These findings provide direct mechanistic evidence for how IDRs tune transcription factor search dynamics and expand sequence recognition beyond canonical motifs, supporting a mechanism for promoter selectivity in complex genomic contexts.

biophysics↗

bioRxiv2019

Prochlorococcus rely on microbial interactions rather than on chlorotic resting stages to survive long-term stress

Many microorganisms produce resting cells with very low metabolic activity that allow them to survive phases of prolonged nutrient or energy stress. In cyanobacteria and some eukaryotic phytoplankton, the production of resting stages is accompanied by a loss of photosynthetic pigments, a process termed chlorosis. Here, we show that a chlorosis-like process occurs under multiple stress conditions in axenic laboratory cultures of Prochlorococcus, the dominant phytoplankton linage in large regions of the oligotrophic ocean and a global key player in ocean biogeochemical cycles. In Prochlorococcus strain MIT9313, chlorotic cells show reduced metabolic activity, measured as C and N uptake by NanoSIMS. However, unlike many other cyanobacteria, chlorotic Prochlorococcus cells are not viable and do not re-grow under axenic conditions when transferred to new media. Nevertheless, co-cultures with a heterotrophic bacterium, Alteromonas macleodii HOT1A3, allowed Prochlorococcus to survive nutrient starvation for months. We propose that reliance on co-occurring heterotrophic bacteria, rather than the ability to survive extended starvation as resting cells, underlies the ecological success of Prochlorococcus. ImportanceThe ability of microorganisms to withstand long periods of nutrient starvation is key to their survival and success under highly fluctuating conditions as is common in nature. Therefore, one would expect this trait to be prevalent among organisms in the nutrient-poor open ocean. Here, we show that this is not the case for Prochlorococcus, a globally abundant and ecologically impactful marine cyanobacterium. Instead, Prochlorococcus rely on co-occurring heterotrophic bacteria to survive extended phases of nutrient and light starvation. Our results highlight the power of microbial interactions to drive major biogeochemical cycles in the ocean and elsewhere with consequences at the global scale.

microbiology↗