Cbp1 and Cren7 form chromatin-like structures that ensure efficient transcription of long CRISPR arrays
Fabian Blombach (),
Michal Sýkora,
Jo Case,
Xu Feng,
Diana P. Baquero,
Thomas Fouqueau,
Duy Khanh Phung,
Declan Barker,
Mart Krupovic,
Qunxin She and
Finn Werner ()
Additional contact information
Fabian Blombach: University College London
Michal Sýkora: University College London
Jo Case: University College London
Xu Feng: Microbial Technology Institute, Shandong University
Diana P. Baquero: Institut Pasteur, Université Paris Cité, CNRS UMR6047, Archaeal Virology Unit
Thomas Fouqueau: University College London
Duy Khanh Phung: University College London
Declan Barker: University College London
Mart Krupovic: Institut Pasteur, Université Paris Cité, CNRS UMR6047, Archaeal Virology Unit
Qunxin She: Microbial Technology Institute, Shandong University
Finn Werner: University College London
Nature Communications, 2024, vol. 15, issue 1, 1-17
Abstract:
Abstract CRISPR arrays form the physical memory of CRISPR adaptive immune systems by incorporating foreign DNA as spacers that are often AT-rich and derived from viruses. As promoter elements such as the TATA-box are AT-rich, CRISPR arrays are prone to harbouring cryptic promoters. Sulfolobales harbour extremely long CRISPR arrays spanning several kilobases, a feature that is accompanied by the CRISPR-specific transcription factor Cbp1. Aberrant Cbp1 expression modulates CRISPR array transcription, but the molecular mechanisms underlying this regulation are unknown. Here, we characterise the genome-wide Cbp1 binding at nucleotide resolution and characterise the binding motifs on distinct CRISPR arrays, as well as on unexpected non-canonical binding sites associated with transposons. Cbp1 recruits Cren7 forming together ‘chimeric’ chromatin-like structures at CRISPR arrays. We dissect Cbp1 function in vitro and in vivo and show that the third helix-turn-helix domain is responsible for Cren7 recruitment, and that Cbp1-Cren7 chromatinization plays a dual role in the transcription of CRISPR arrays. It suppresses spurious transcription from cryptic promoters within CRISPR arrays but enhances CRISPR RNA transcription directed from their cognate promoters in their leader region. Our results show that Cbp1-Cren7 chromatinization drives the productive expression of long CRISPR arrays.
Date: 2024
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-45728-8
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DOI: 10.1038/s41467-024-45728-8
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