Model-driven Mapping of Transcriptional Networks Reveals the Circuitry and Dynamics of Virulence Regulation

Overview

Journal Genome Res

Specialty Genetics

Date 2015 Feb 4

PMID 25644834

Citations 35

Authors

Ezekiel J Maier

Brian C Haynes

Stacey R Gish

Zhuo A Wang

Michael L Skowyra

Alyssa L Marulli

Tamara L Doering

Michael R Brent

Affiliations

Soon will be listed here.

Abstract

Key steps in understanding a biological process include identifying genes that are involved and determining how they are regulated. We developed a novel method for identifying transcription factors (TFs) involved in a specific process and used it to map regulation of the key virulence factor of a deadly fungus-its capsule. The map, built from expression profiles of 41 TF mutants, includes 20 TFs not previously known to regulate virulence attributes. It also reveals a hierarchy comprising executive, midlevel, and "foreman" TFs. When grouped by temporal expression pattern, these TFs explain much of the transcriptional dynamics of capsule induction. Phenotypic analysis of TF deletion mutants revealed complex relationships among virulence factors and virulence in mice. These resources and analyses provide the first integrated, systems-level view of capsule regulation and biosynthesis. Our methods dramatically improve the efficiency with which transcriptional networks can be analyzed, making genomic approaches accessible to laboratories focused on specific physiological processes.

Citing Articles

Leveraging a new data resource to define the response of Cryptococcus neoformans to environmental signals.

Kang Y, Jung J, Brown H, Mateusiak C, Doering T, Brent M Genetics. 2024; 229(1):1-29.

PMID: 39485829 PMC: 11708910. DOI: 10.1093/genetics/iyae178.

A Quick reCAP: Discovering Capsule Mutants.

Boodwa-Ko D, Doering T J Fungi (Basel). 2024; 10(2).

PMID: 38392786 PMC: 10889740. DOI: 10.3390/jof10020114.

CryptoCEN: A Co-Expression Network for Cryptococcus neoformans reveals novel proteins involved in DNA damage repair.

OMeara M, Rapala J, Nichols C, Alexandre A, Billmyre R, Steenwyk J PLoS Genet. 2024; 20(2):e1011158.

PMID: 38359090 PMC: 10901339. DOI: 10.1371/journal.pgen.1011158.

Unbiased discovery of natural sequence variants that influence fungal virulence.

Agustinho D, Brown H, Chen G, Gaylord E, Geddes-McAlister J, Brent M Cell Host Microbe. 2023; 31(11):1910-1920.e5.

PMID: 37898126 PMC: 10842055. DOI: 10.1016/j.chom.2023.10.002.

CryptoCEN: A Co-Expression Network for reveals novel proteins involved in DNA damage repair.

OMeara M, Rapala J, Nichols C, Alexandre C, Billmyre R, Steenwyk J bioRxiv. 2023; .

PMID: 37645941 PMC: 10462067. DOI: 10.1101/2023.08.17.553567.

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