Bromodomain factor 5 is an essential regulator of transcription in Leishmania.

Autor: Jones NG; York Biomedical Research Institute, Department of Biology, University of York, York, UK. nathaniel.jones@york.ac.uk., Geoghegan V; York Biomedical Research Institute, Department of Biology, University of York, York, UK., Moore G; York Biomedical Research Institute, Department of Biology, University of York, York, UK., Carnielli JBT; York Biomedical Research Institute, Department of Biology, University of York, York, UK., Newling K; York Biomedical Research Institute, Department of Biology, University of York, York, UK., Calderón F; GSK Global Health, Tres Cantos, 28760, Madrid, Spain., Gabarró R; GSK Global Health, Tres Cantos, 28760, Madrid, Spain., Martín J; GSK Global Health, Tres Cantos, 28760, Madrid, Spain., Prinjha RK; Immunology Research Unit, Research, R&D GSK, Gunnels Wood Road, Stevenage, Herts, SG1 2NY, UK., Rioja I; Immunology Research Unit, Research, R&D GSK, Gunnels Wood Road, Stevenage, Herts, SG1 2NY, UK., Wilkinson AJ; York Biomedical Research Institute and York Structural Biology Laboratory, Department of Chemistry, University of York, York, UK., Mottram JC; York Biomedical Research Institute, Department of Biology, University of York, York, UK.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2022 Jul 13; Vol. 13 (1), pp. 4071. Date of Electronic Publication: 2022 Jul 13.
DOI: 10.1038/s41467-022-31742-1
Abstrakt: Leishmania are unicellular parasites that cause human and animal diseases. Like other kinetoplastids, they possess large transcriptional start regions (TSRs) which are defined by histone variants and histone lysine acetylation. Cellular interpretation of these chromatin marks is not well understood. Eight bromodomain factors, the reader modules for acetyl-lysine, are found across Leishmania genomes. Using L. mexicana, Cas9-driven gene deletions indicate that BDF1-5 are essential for promastigotes. Dimerisable, split Cre recombinase (DiCre)-inducible gene deletion of BDF5 show it is essential for both promastigotes and murine infection. ChIP-seq identifies BDF5 as enriched at TSRs. XL-BioID proximity proteomics shows the BDF5 landscape is enriched for BDFs, HAT2, proteins involved in transcriptional activity, and RNA processing; revealing a Conserved Regulators of Kinetoplastid Transcription (CRKT) Complex. Inducible deletion of BDF5 causes global reduction in RNA polymerase II transcription. Our results indicate the requirement of Leishmania to interpret histone acetylation marks through the bromodomain-enriched CRKT complex for normal gene expression and cellular viability.
(© 2022. The Author(s).)
Databáze: MEDLINE
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