PAS Domain Protein Pas3 Interacts with the Chromatin Modifier Bre1 in Regulating Cryptococcal Morphogenesis

ABSTRACT Switching between different morphotypes is an adaptive cellular response in many microbes. In Cryptococcus neoformans, the yeast-to-hypha transition confers resistance to microbial predation in the soil and is an integral part of its life cycle. Morphogenesis is also known to be associated...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Youbao Zhao, Srijana Upadhyay, Xiaorong Lin
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2018
Materias:	morphogenesis PAS domain histone modification epigenetic mating subcellular localization Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/581e82fdaa3a4cb385a08fca4634149e
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:581e82fdaa3a4cb385a08fca4634149e
record_format	dspace
spelling	oai:doaj.org-article:581e82fdaa3a4cb385a08fca4634149e2021-11-15T15:52:20ZPAS Domain Protein Pas3 Interacts with the Chromatin Modifier Bre1 in Regulating Cryptococcal Morphogenesis10.1128/mBio.02135-182150-7511https://doaj.org/article/581e82fdaa3a4cb385a08fca4634149e2018-12-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.02135-18https://doaj.org/toc/2150-7511ABSTRACT Switching between different morphotypes is an adaptive cellular response in many microbes. In Cryptococcus neoformans, the yeast-to-hypha transition confers resistance to microbial predation in the soil and is an integral part of its life cycle. Morphogenesis is also known to be associated with virulence, with the filamentous form being immune-stimulatory and protective in mammalian models of cryptococcosis. Previous studies identified the transcription factor Znf2 as a master regulator of cryptococcal filamentation. However, the upstream regulators of Znf2 remain largely unknown. PAS domain proteins have long been recognized as transducers of diverse environmental signals. Here, we identified a PAS domain protein Pas3 as an upstream regulator of Znf2. Surprisingly, this small Pas3 protein lacks a nuclear localization signal but is enriched in the nucleus where it regulates the transcript level of ZNF2 and its prominent downstream targets. We discovered that the PAS domain is essential for Pas3’s nuclear enrichment and function. Intriguingly, Pas3 interacts with Bre1, which is required for Cryptococcus histone H2B monoubiquitination (H2Bub1) and H3 lysine 4 dimethylation (H3K4me2), two histone modifications known to be associated with active gene transcription. Indeed, Bre1 functions together with Pas3 in regulating cryptococcal filamentation based on loss-of-function, epistasis, and transcriptome analysis. These findings provide the first evidence of a signaling regulator acting with a chromatin modifier to control cryptococcal filamentation. IMPORTANCE For the ubiquitous environmental pathogen Cryptococcus neoformans, the morphological transition from yeast to filament confers resistance to natural predators like soil amoeba and is an integral differentiation event to produce infectious spores. Interestingly, filamentation is immuno-stimulatory and attenuates cryptococcal virulence in a mammalian host. Consistently, the morphogenesis transcription factor Znf2 profoundly shapes cryptococcal interaction with various hosts. Identifying the signaling pathways activating filamentation is thus, conductive to a better understanding of cryptococcal biology. In this study, we identified a PAS domain protein Pas3 that functions upstream of Znf2 in regulating cryptococcal filamentation. Interestingly, Pas3 interacts with the chromatin modifier Bre1 in the nucleus to regulate the transcript level of Znf2 and its prominent downstream targets. This is the first example of a PAS domain signaling regulator interacting with a chromatin modifier to control filamentation through their impact on cryptococcal transcriptome.Youbao ZhaoSrijana UpadhyayXiaorong LinAmerican Society for MicrobiologyarticlemorphogenesisPAS domainhistone modificationepigeneticmatingsubcellular localizationMicrobiologyQR1-502ENmBio, Vol 9, Iss 6 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	morphogenesis PAS domain histone modification epigenetic mating subcellular localization Microbiology QR1-502
spellingShingle	morphogenesis PAS domain histone modification epigenetic mating subcellular localization Microbiology QR1-502 Youbao Zhao Srijana Upadhyay Xiaorong Lin PAS Domain Protein Pas3 Interacts with the Chromatin Modifier Bre1 in Regulating Cryptococcal Morphogenesis
description	ABSTRACT Switching between different morphotypes is an adaptive cellular response in many microbes. In Cryptococcus neoformans, the yeast-to-hypha transition confers resistance to microbial predation in the soil and is an integral part of its life cycle. Morphogenesis is also known to be associated with virulence, with the filamentous form being immune-stimulatory and protective in mammalian models of cryptococcosis. Previous studies identified the transcription factor Znf2 as a master regulator of cryptococcal filamentation. However, the upstream regulators of Znf2 remain largely unknown. PAS domain proteins have long been recognized as transducers of diverse environmental signals. Here, we identified a PAS domain protein Pas3 as an upstream regulator of Znf2. Surprisingly, this small Pas3 protein lacks a nuclear localization signal but is enriched in the nucleus where it regulates the transcript level of ZNF2 and its prominent downstream targets. We discovered that the PAS domain is essential for Pas3’s nuclear enrichment and function. Intriguingly, Pas3 interacts with Bre1, which is required for Cryptococcus histone H2B monoubiquitination (H2Bub1) and H3 lysine 4 dimethylation (H3K4me2), two histone modifications known to be associated with active gene transcription. Indeed, Bre1 functions together with Pas3 in regulating cryptococcal filamentation based on loss-of-function, epistasis, and transcriptome analysis. These findings provide the first evidence of a signaling regulator acting with a chromatin modifier to control cryptococcal filamentation. IMPORTANCE For the ubiquitous environmental pathogen Cryptococcus neoformans, the morphological transition from yeast to filament confers resistance to natural predators like soil amoeba and is an integral differentiation event to produce infectious spores. Interestingly, filamentation is immuno-stimulatory and attenuates cryptococcal virulence in a mammalian host. Consistently, the morphogenesis transcription factor Znf2 profoundly shapes cryptococcal interaction with various hosts. Identifying the signaling pathways activating filamentation is thus, conductive to a better understanding of cryptococcal biology. In this study, we identified a PAS domain protein Pas3 that functions upstream of Znf2 in regulating cryptococcal filamentation. Interestingly, Pas3 interacts with the chromatin modifier Bre1 in the nucleus to regulate the transcript level of Znf2 and its prominent downstream targets. This is the first example of a PAS domain signaling regulator interacting with a chromatin modifier to control filamentation through their impact on cryptococcal transcriptome.
format	article
author	Youbao Zhao Srijana Upadhyay Xiaorong Lin
author_facet	Youbao Zhao Srijana Upadhyay Xiaorong Lin
author_sort	Youbao Zhao
title	PAS Domain Protein Pas3 Interacts with the Chromatin Modifier Bre1 in Regulating Cryptococcal Morphogenesis
title_short	PAS Domain Protein Pas3 Interacts with the Chromatin Modifier Bre1 in Regulating Cryptococcal Morphogenesis
title_full	PAS Domain Protein Pas3 Interacts with the Chromatin Modifier Bre1 in Regulating Cryptococcal Morphogenesis
title_fullStr	PAS Domain Protein Pas3 Interacts with the Chromatin Modifier Bre1 in Regulating Cryptococcal Morphogenesis
title_full_unstemmed	PAS Domain Protein Pas3 Interacts with the Chromatin Modifier Bre1 in Regulating Cryptococcal Morphogenesis
title_sort	pas domain protein pas3 interacts with the chromatin modifier bre1 in regulating cryptococcal morphogenesis
publisher	American Society for Microbiology
publishDate	2018
url	https://doaj.org/article/581e82fdaa3a4cb385a08fca4634149e
work_keys_str_mv	AT youbaozhao pasdomainproteinpas3interactswiththechromatinmodifierbre1inregulatingcryptococcalmorphogenesis AT srijanaupadhyay pasdomainproteinpas3interactswiththechromatinmodifierbre1inregulatingcryptococcalmorphogenesis AT xiaoronglin pasdomainproteinpas3interactswiththechromatinmodifierbre1inregulatingcryptococcalmorphogenesis
_version_	1718427276772638720

PAS Domain Protein Pas3 Interacts with the Chromatin Modifier Bre1 in Regulating Cryptococcal Morphogenesis

Ejemplares similares