Chromatin Profiling of the Repetitive and Nonrepetitive Genomes of the Human Fungal Pathogen <named-content content-type="genus-species">Candida albicans</named-content>

ABSTRACT Eukaryotic genomes are packaged into chromatin structures that play pivotal roles in regulating all DNA-associated processes. Histone posttranslational modifications modulate chromatin structure and function, leading to rapid regulation of gene expression and genome stability, key steps in...

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Main Authors: Robert Jordan Price, Esther Weindling, Judith Berman, Alessia Buscaino
Format: Article
Language:English
Published: American Society for Microbiology 2019-08-01
Series:mBio
Subjects:
Online Access:https://journals.asm.org/doi/10.1128/mBio.01376-19
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author Robert Jordan Price
Esther Weindling
Judith Berman
Alessia Buscaino
author_facet Robert Jordan Price
Esther Weindling
Judith Berman
Alessia Buscaino
author_sort Robert Jordan Price
collection DOAJ
description ABSTRACT Eukaryotic genomes are packaged into chromatin structures that play pivotal roles in regulating all DNA-associated processes. Histone posttranslational modifications modulate chromatin structure and function, leading to rapid regulation of gene expression and genome stability, key steps in environmental adaptation. Candida albicans, a prevalent fungal pathogen in humans, can rapidly adapt and thrive in diverse host niches. The contribution of chromatin to C. albicans biology is largely unexplored. Here, we generated the first comprehensive chromatin profile of histone modifications (histone H3 trimethylated on lysine 4 [H3K4me3], histone H3 acetylated on lysine 9 [H3K9Ac], acetylated lysine 16 on histone H4 [H4K16Ac], and γH2A) across the C. albicans genome and investigated its relationship to gene expression by harnessing genome-wide sequencing approaches. We demonstrated that gene-rich nonrepetitive regions are packaged into canonical euchromatin in association with histone modifications that mirror their transcriptional activity. In contrast, repetitive regions are assembled into distinct chromatin states; subtelomeric regions and the ribosomal DNA (rDNA) locus are assembled into heterochromatin, while major repeat sequences and transposons are packaged in chromatin that bears features of euchromatin and heterochromatin. Genome-wide mapping of γH2A, a marker of genome instability, identified potential recombination-prone genomic loci. Finally, we present the first quantitative chromatin profiling in C. albicans to delineate the role of the chromatin modifiers Sir2 and Set1 in controlling chromatin structure and gene expression. This report presents the first genome-wide chromatin profiling of histone modifications associated with the C. albicans genome. These epigenomic maps provide an invaluable resource to understand the contribution of chromatin to C. albicans biology and identify aspects of C. albicans chromatin organization that differ from that of other yeasts. IMPORTANCE The fungus Candida albicans is an opportunistic pathogen that normally lives on the human body without causing any harm. However, C. albicans is also a dangerous pathogen responsible for millions of infections annually. C. albicans is such a successful pathogen because it can adapt to and thrive in different environments. Chemical modifications of chromatin, the structure that packages DNA into cells, can allow environmental adaptation by regulating gene expression and genome organization. Surprisingly, the contribution of chromatin modification to C. albicans biology is still largely unknown. For the first time, we analyzed C. albicans chromatin modifications on a genome-wide basis. We demonstrate that specific chromatin states are associated with distinct regions of the C. albicans genome and identify the roles of the chromatin modifiers Sir2 and Set1 in shaping C. albicans chromatin and gene expression.
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spelling doaj.art-0e94037294e0404bafe7fa0e40958e8e2022-12-21T19:53:56ZengAmerican Society for MicrobiologymBio2150-75112019-08-0110410.1128/mBio.01376-19Chromatin Profiling of the Repetitive and Nonrepetitive Genomes of the Human Fungal Pathogen <named-content content-type="genus-species">Candida albicans</named-content>Robert Jordan Price0Esther Weindling1Judith Berman2Alessia Buscaino3Kent Fungal Group, School of Biosciences, University of Kent, Canterbury, Kent, United KingdomDepartment of Microbiology and Biotechnology, George S. Wise Faculty of Life Sciences, Tel Aviv University, Ramat Aviv, IsraelDepartment of Microbiology and Biotechnology, George S. Wise Faculty of Life Sciences, Tel Aviv University, Ramat Aviv, IsraelKent Fungal Group, School of Biosciences, University of Kent, Canterbury, Kent, United KingdomABSTRACT Eukaryotic genomes are packaged into chromatin structures that play pivotal roles in regulating all DNA-associated processes. Histone posttranslational modifications modulate chromatin structure and function, leading to rapid regulation of gene expression and genome stability, key steps in environmental adaptation. Candida albicans, a prevalent fungal pathogen in humans, can rapidly adapt and thrive in diverse host niches. The contribution of chromatin to C. albicans biology is largely unexplored. Here, we generated the first comprehensive chromatin profile of histone modifications (histone H3 trimethylated on lysine 4 [H3K4me3], histone H3 acetylated on lysine 9 [H3K9Ac], acetylated lysine 16 on histone H4 [H4K16Ac], and γH2A) across the C. albicans genome and investigated its relationship to gene expression by harnessing genome-wide sequencing approaches. We demonstrated that gene-rich nonrepetitive regions are packaged into canonical euchromatin in association with histone modifications that mirror their transcriptional activity. In contrast, repetitive regions are assembled into distinct chromatin states; subtelomeric regions and the ribosomal DNA (rDNA) locus are assembled into heterochromatin, while major repeat sequences and transposons are packaged in chromatin that bears features of euchromatin and heterochromatin. Genome-wide mapping of γH2A, a marker of genome instability, identified potential recombination-prone genomic loci. Finally, we present the first quantitative chromatin profiling in C. albicans to delineate the role of the chromatin modifiers Sir2 and Set1 in controlling chromatin structure and gene expression. This report presents the first genome-wide chromatin profiling of histone modifications associated with the C. albicans genome. These epigenomic maps provide an invaluable resource to understand the contribution of chromatin to C. albicans biology and identify aspects of C. albicans chromatin organization that differ from that of other yeasts. IMPORTANCE The fungus Candida albicans is an opportunistic pathogen that normally lives on the human body without causing any harm. However, C. albicans is also a dangerous pathogen responsible for millions of infections annually. C. albicans is such a successful pathogen because it can adapt to and thrive in different environments. Chemical modifications of chromatin, the structure that packages DNA into cells, can allow environmental adaptation by regulating gene expression and genome organization. Surprisingly, the contribution of chromatin modification to C. albicans biology is still largely unknown. For the first time, we analyzed C. albicans chromatin modifications on a genome-wide basis. We demonstrate that specific chromatin states are associated with distinct regions of the C. albicans genome and identify the roles of the chromatin modifiers Sir2 and Set1 in shaping C. albicans chromatin and gene expression.https://journals.asm.org/doi/10.1128/mBio.01376-19Candida albicanseuchromatingenome instabilityheterochromatinchromatinepigenetics
spellingShingle Robert Jordan Price
Esther Weindling
Judith Berman
Alessia Buscaino
Chromatin Profiling of the Repetitive and Nonrepetitive Genomes of the Human Fungal Pathogen <named-content content-type="genus-species">Candida albicans</named-content>
mBio
Candida albicans
euchromatin
genome instability
heterochromatin
chromatin
epigenetics
title Chromatin Profiling of the Repetitive and Nonrepetitive Genomes of the Human Fungal Pathogen <named-content content-type="genus-species">Candida albicans</named-content>
title_full Chromatin Profiling of the Repetitive and Nonrepetitive Genomes of the Human Fungal Pathogen <named-content content-type="genus-species">Candida albicans</named-content>
title_fullStr Chromatin Profiling of the Repetitive and Nonrepetitive Genomes of the Human Fungal Pathogen <named-content content-type="genus-species">Candida albicans</named-content>
title_full_unstemmed Chromatin Profiling of the Repetitive and Nonrepetitive Genomes of the Human Fungal Pathogen <named-content content-type="genus-species">Candida albicans</named-content>
title_short Chromatin Profiling of the Repetitive and Nonrepetitive Genomes of the Human Fungal Pathogen <named-content content-type="genus-species">Candida albicans</named-content>
title_sort chromatin profiling of the repetitive and nonrepetitive genomes of the human fungal pathogen named content content type genus species candida albicans named content
topic Candida albicans
euchromatin
genome instability
heterochromatin
chromatin
epigenetics
url https://journals.asm.org/doi/10.1128/mBio.01376-19
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