Multi-omic regulatory networks capture downstream effects of kinase inhibition in Mycobacterium tuberculosis

Abstract The ability of Mycobacterium tuberculosis (Mtb) to adapt to diverse stresses in its host environment is crucial for pathogenesis. Two essential Mtb serine/threonine protein kinases, PknA and PknB, regulate cell growth in response to environmental stimuli, but little is known about their dow...

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Autores principales:	Albert T. Young, Xavier Carette, Michaela Helmel, Hanno Steen, Robert N. Husson, John Quackenbush, John Platig
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/2df1222b97bb43faa8f378b2567a1374
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spelling	oai:doaj.org-article:2df1222b97bb43faa8f378b2567a13742021-12-02T13:57:39ZMulti-omic regulatory networks capture downstream effects of kinase inhibition in Mycobacterium tuberculosis10.1038/s41540-020-00164-42056-7189https://doaj.org/article/2df1222b97bb43faa8f378b2567a13742021-01-01T00:00:00Zhttps://doi.org/10.1038/s41540-020-00164-4https://doaj.org/toc/2056-7189Abstract The ability of Mycobacterium tuberculosis (Mtb) to adapt to diverse stresses in its host environment is crucial for pathogenesis. Two essential Mtb serine/threonine protein kinases, PknA and PknB, regulate cell growth in response to environmental stimuli, but little is known about their downstream effects. By combining RNA-Seq data, following treatment with either an inhibitor of both PknA and PknB or an inactive control, with publicly available ChIP-Seq and protein–protein interaction data for transcription factors, we show that the Mtb transcription factor (TF) regulatory network propagates the effects of kinase inhibition and leads to widespread changes in regulatory programs involved in cell wall integrity, stress response, and energy production, among others. We also observe that changes in TF regulatory activity correlate with kinase-specific phosphorylation of those TFs. In addition to characterizing the downstream regulatory effects of PknA/PknB inhibition, this demonstrates the need for regulatory network approaches that can incorporate signal-driven transcription factor modifications.Albert T. YoungXavier CaretteMichaela HelmelHanno SteenRobert N. HussonJohn QuackenbushJohn PlatigNature PortfolioarticleBiology (General)QH301-705.5ENnpj Systems Biology and Applications, Vol 7, Iss 1, Pp 1-7 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Biology (General) QH301-705.5
spellingShingle	Biology (General) QH301-705.5 Albert T. Young Xavier Carette Michaela Helmel Hanno Steen Robert N. Husson John Quackenbush John Platig Multi-omic regulatory networks capture downstream effects of kinase inhibition in Mycobacterium tuberculosis
description	Abstract The ability of Mycobacterium tuberculosis (Mtb) to adapt to diverse stresses in its host environment is crucial for pathogenesis. Two essential Mtb serine/threonine protein kinases, PknA and PknB, regulate cell growth in response to environmental stimuli, but little is known about their downstream effects. By combining RNA-Seq data, following treatment with either an inhibitor of both PknA and PknB or an inactive control, with publicly available ChIP-Seq and protein–protein interaction data for transcription factors, we show that the Mtb transcription factor (TF) regulatory network propagates the effects of kinase inhibition and leads to widespread changes in regulatory programs involved in cell wall integrity, stress response, and energy production, among others. We also observe that changes in TF regulatory activity correlate with kinase-specific phosphorylation of those TFs. In addition to characterizing the downstream regulatory effects of PknA/PknB inhibition, this demonstrates the need for regulatory network approaches that can incorporate signal-driven transcription factor modifications.
format	article
author	Albert T. Young Xavier Carette Michaela Helmel Hanno Steen Robert N. Husson John Quackenbush John Platig
author_facet	Albert T. Young Xavier Carette Michaela Helmel Hanno Steen Robert N. Husson John Quackenbush John Platig
author_sort	Albert T. Young
title	Multi-omic regulatory networks capture downstream effects of kinase inhibition in Mycobacterium tuberculosis
title_short	Multi-omic regulatory networks capture downstream effects of kinase inhibition in Mycobacterium tuberculosis
title_full	Multi-omic regulatory networks capture downstream effects of kinase inhibition in Mycobacterium tuberculosis
title_fullStr	Multi-omic regulatory networks capture downstream effects of kinase inhibition in Mycobacterium tuberculosis
title_full_unstemmed	Multi-omic regulatory networks capture downstream effects of kinase inhibition in Mycobacterium tuberculosis
title_sort	multi-omic regulatory networks capture downstream effects of kinase inhibition in mycobacterium tuberculosis
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/2df1222b97bb43faa8f378b2567a1374
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Multi-omic regulatory networks capture downstream effects of kinase inhibition in Mycobacterium tuberculosis

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