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bioRxiv · 10.1101/2025.11.30.691466

An Lrs14 family protein functions as a nucleoid-associated protein regulating cell cycle progression in Sulfolobales

Gan, Q.·Li, H.·Huang, Q.·Yang, Y.·Sun, F.·Feng, X.·Ni, J.·Zhang, Z.·She, Q.·Shen, Y.
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Abstract

Archaea of the order Sulfolobales possess eukaryotic-like cell cycle. The chromatin organization in these archaea is supposed to rely on nucleoid-associated proteins (NAPs). Genomes of Sulfolobales species encode multiple members of the Lrs14 protein family, which have been postulated to function as NAPs. Here, we show that one of the Lrs14 family protein, named Sul14a, is a potential key player in dynamic chromatin organization in Saccharolobus islandicus. Sul14a is transcribed in a cell cycle-dependent manner and appears to be essential for cell viability. The protein exhibits DNA-binding activity preferring AT-rich sequences and can bridge DNA in vitro. ChIP-seq analysis revealed that Sul14a is enriched at AT-rich regions of the chromatin. Overexpression of Sul14a leads to cell cycle arrest at G2 phase. High-throughput chromosome conformation capture (Hi-C) and transcriptomic analyses indicate that Sul14a overexpression results in chromatin contact reduction and global transcriptional changes. In addition, we observed that the chromatin contact pattern changes markedly between 1h and 5h after release from G2 synchronization, corresponding to the lowest and highest levels of sul14a transcription, respectively, during the cell cycle. Our results establish that Sul14a is an NAP intimately associated with chromatin dynamics and global transcriptional changes during the cell cycle in Sulfolobales.

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Gan, Q., Li, H., Huang, Q., Yang, Y., Sun, F., Feng, X., Ni, J., Zhang, Z., She, Q., Shen, Y.. 2025-12-01. An Lrs14 family protein functions as a nucleoid-associated protein regulating cell cycle progression in Sulfolobales. https://doi.org/10.1101/2025.11.30.691466

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