The YEATS Domain Histone Crotonylation Readers Control Virulence-Related Biology of a Major Human Pathogen

Wang, Qi; Verma, Jiyoti; Vidan, Nikolina; Wang, Yanan; Tucey, Timothy M.; Lo, Tricia L.; Harrison, Paul F.; See, Michael; Swaminathan, Angavai; Kuchler, Karl; Tscherner, Michael; Song, Jiangning; Powell, David R.; Sopta, Mary; Traven, Ana

doi:10.1016/j.celrep.2020.107528

Cited by 20 publications

(26 citation statements)

References 63 publications

(83 reference statements)

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Section: The Functions Of Kcr In Microbiologymentioning

confidence: 99%

“…Histone crotonylation in pathogenic Candida albicans was dynamically controlled by metabolism and stress responses [ 72 ]. Crotonate can regulate responsive transcriptional program and result in resistance against cell wall stress [ 72 ]. Taf14 is essential for Candida albicans virulence by controlling gene expression, stress resistance and invasive growth via its chromatin reader function [ 72 ].…”

Section: The Functions Of Kcr In Microbiologymentioning

confidence: 99%

“…Crotonate can regulate responsive transcriptional program and result in resistance against cell wall stress [ 72 ]. Taf14 is essential for Candida albicans virulence by controlling gene expression, stress resistance and invasive growth via its chromatin reader function [ 72 ]. Crotonylome analysis in Candida albicans displayed that majority of crotonylated proteins were involved in biosynthetic events and carbon metabolism [ 73 ].…”

Section: The Functions Of Kcr In Microbiologymentioning

confidence: 99%

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Protein lysine crotonylation: past, present, perspective

Jiang

Lü

et al. 2021

Cell Death Dis

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Lysine crotonylation has been discovered in histone and non-histone proteins and found to be involved in diverse diseases and biological processes, such as neuropsychiatric disease, carcinogenesis, spermatogenesis, tissue injury, and inflammation. The unique carbon–carbon π-bond structure indicates that lysine crotonylation may use distinct regulatory mechanisms from the widely studied other types of lysine acylation. In this review, we discussed the regulation of lysine crotonylation by enzymatic and non-enzymatic mechanisms, the recognition of substrate proteins, the physiological functions of lysine crotonylation and its cross-talk with other types of modification. The tools and methods for prediction and detection of lysine crotonylation were also described.

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Section: The Functions Of Kcr In Microbiologymentioning

confidence: 99%

Section: The Functions Of Kcr In Microbiologymentioning

confidence: 99%

Section: The Functions Of Kcr In Microbiologymentioning

confidence: 99%

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Protein lysine crotonylation: past, present, perspective

Jiang

Lü

et al. 2021

Cell Death Dis

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“…As such, several of the 50 auxiliary transcriptional regulators are integrated into the larger biofilm network that includes the core nine transcriptional regulators and all of their directly bound target genes (Nobile et al, 2012). Based on existing phenotypic analyses of the mutant strains of the auxiliary biofilm transcriptional regulators, the majority (48) are implicated in the regulation of adhesion and/or filamentation (Brown et al, 1999;Kadosh and Johnson, 2001;Cheng et al, 2003;Uhl et al, 2003;Garcıá-Sańchez et al, 2004;Kelly et al, 2004;Mulhern et al, 2006;Kim et al, 2008b;Shen et al, 2008;Wheeler et al, 2008;Homann et al, 2009;Nobile et al, 2009;Pukkila-Worley et al, 2009;Uppuluri et al, 2010a;Uppuluri et al, 2010b;Askew et al, 2011;Bonhomme et al, 2011;Ganguly et al, 2011;Finkel et al, 2012;Kamthan et al, 2012;Langford et al, 2013;Delgado-Silva et al, 2014;Tsai et al, 2014;Chen and Lan, 2015;Fox et al, 2015;Ghosh et al, 2015;Kakade et al, 2016;Kakade et al, 2019;Böttcher et al, 2020;Lagree et al, 2020;Omran et al, 2020;Wang et al, 2020); 16 are implicated in drug resistance and/or tolerance (Bruno et al, 2006;Cornet et al, 2006;Mulhern et al, 2006;Xu et al, 2007;…”

Section: Regulation Of Biofilm Formationmentioning

confidence: 99%

Transcriptional Circuits Regulating Developmental Processes in Candida albicans

Rodriguez

Quail

Hernday

et al. 2020

Front. Cell. Infect. Microbiol.

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Candida albicans is a commensal member of the human microbiota that colonizes multiple niches in the body including the skin, oral cavity, and gastrointestinal and genitourinary tracts of healthy individuals. It is also the most common human fungal pathogen isolated from patients in clinical settings. C. albicans can cause a number of superficial and invasive infections, especially in immunocompromised individuals. The ability of C. albicans to succeed as both a commensal and a pathogen, and to thrive in a wide range of environmental niches within the host, requires sophisticated transcriptional regulatory programs that can integrate and respond to host specific environmental signals. Identifying and characterizing the transcriptional regulatory networks that control important developmental processes in C. albicans will shed new light on the strategies used by C. albicans to colonize and infect its host. Here, we discuss the transcriptional regulatory circuits controlling three major developmental processes in C. albicans: biofilm formation, the white-opaque phenotypic switch, and the commensal-pathogen transition. Each of these three circuits are tightly knit and, through our analyses, we show that they are integrated together by extensive regulatory crosstalk between the core regulators that comprise each circuit.

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“…For fungal burdens ( Fig 6B ), the rsc4 ΔΔ mutant and rsc4 ΔΔ+ RSC4 complemented strain were assayed alongside several other mutants and the parental wild type strain. The fungal burden data for the parental wild type was published alongside the other mutants elsewhere [ 63 ]. Importantly, the fungal burden for the rsc4 ΔΔ+ RSC4 complemented strain was equivalent to the wild type strain (p = 0.994).…”

Section: Methodsmentioning

confidence: 99%

The RSC (Remodels the Structure of Chromatin) complex of Candida albicans shows compositional divergence with distinct roles in regulating pathogenic traits

et al. 2020

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Regulation of gene expression programs is crucial for the survival of microbial pathogens in host environments and for their ability to cause disease. Here we investigated the epigenetic regulator RSC (Remodels the Structure of Chromatin) in the most prevalent human fungal pathogen Candida albicans. Biochemical analysis showed that CaRSC comprises 13 subunits and contains two novel non-essential members, which we named Nri1 and Nri2 (Novel RSC Interactors) that are exclusive to the CTG clade of Saccharomycotina. Genetic analysis showed distinct essentiality of C. albicans RSC subunits compared to model fungal species suggesting functional and structural divergence of RSC functions in this fungal pathogen. Transcriptomic and proteomic profiling of a conditional mutant of the essential catalytic subunit gene STH1 demonstrated global roles of RSC in C. albicans biology, with the majority of growth-related processes affected, as well as mis-regulation of genes involved in morphotype switching, host-pathogen interaction and adaptive fitness. We further assessed the functions of non-essential CaRSC subunits, showing that the novel subunit Nri1 and the bromodomain subunit Rsc4 play roles in filamentation and stress responses; and also interacted at the genetic level to regulate cell viability. Consistent with these roles, Rsc4 is required for full virulence of C. albicans in the murine model of systemic infection. Taken together, our data builds the first comprehensive study of the composition and roles of RSC in C. albicans, showing both conserved and distinct features compared to model fungal systems. The study illuminates how C. albicans uses RSC-dependent transcriptional regulation to respond to environmental signals and drive survival fitness and virulence in mammals.

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The YEATS Domain Histone Crotonylation Readers Control Virulence-Related Biology of a Major Human Pathogen

Cited by 20 publications

References 63 publications

Protein lysine crotonylation: past, present, perspective

Protein lysine crotonylation: past, present, perspective

Transcriptional Circuits Regulating Developmental Processes in Candida albicans

The RSC (Remodels the Structure of Chromatin) complex of Candida albicans shows compositional divergence with distinct roles in regulating pathogenic traits

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