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

Area of Science:

• Microbiology
• Cellular Biology
• Molecular Biology

Background:

• Cryptococcus neoformans exhibits morphological switching (yeast-to-hypha) for survival and virulence.
• The transcription factor Znf2 is a known master regulator of filamentation.
• Upstream regulators of Znf2 and cryptococcal morphogenesis are largely uncharacterized.

Purpose of the Study:

• To identify novel upstream regulators of Znf2 and cryptococcal filamentation.
• To elucidate the molecular mechanisms controlling the yeast-to-hypha transition in C. neoformans.

Main Methods:

• Identification of a PAS domain protein, Pas3, as a regulator of Znf2.
• Analysis of Pas3's nuclear localization and function, including its PAS domain.
• Investigation of Pas3's interaction with the chromatin modifier Bre1.
• Loss-of-function, epistasis, and transcriptome analyses to assess Bre1 and Pas3 function.

Main Results:

• Pas3 is enriched in the nucleus and regulates ZNF2 transcript levels.
• The PAS domain of Pas3 is critical for its nuclear localization and function.
• Pas3 interacts with Bre1, a protein involved in histone modifications (H2Bub1, H3K4me2).
• Pas3 and Bre1 function together in regulating cryptococcal filamentation.

Conclusions:

• Pas3 is a novel upstream regulator of Znf2, controlling cryptococcal filamentation.
• Pas3 acts in concert with the chromatin modifier Bre1 to regulate gene transcription.
• This study reveals a new signaling pathway involving a PAS domain protein and a chromatin modifier controlling fungal morphogenesis.