Evidence of a Demethylase-Independent Role for the H3K4-Specific Histone Demethylases in Aspergillus nidulans and Fusarium graminearum Secondary Metabolism

Simone Bachleitner, Jens Laurids Sørensen, Agnieszka Gacek-Matthews, Michael Sulyok, Lena Studt, Joseph Strauss

Research output: Contribution to journalJournal articleResearchpeer-review

Abstract

Fungi produce a plethora of secondary metabolites (SMs) involved in cellular protection, defense, and signaling. Like other metabolic processes, transcription of SM biosynthesis genes is tightly regulated to prevent an unnecessary use of resources. Genes involved in SM biosynthesis are usually physically linked, arranged in secondary metabolite gene clusters (SMGCs). Research over the last decades has shown that chromatin structure and posttranslational modifications (PTMs) of histones represent important layers of SMGC regulation. For instance, trimethylation of histone H3 lysine 4 (H3K4me3) is a PTM typically associated with promoter regions of actively transcribed genes. Previously, we have shown that the H3K4me3-specific, JmjC domain-containing histone demethylase KdmB functions not only in repression but also in activation of secondary metabolism in Aspergillus nidulans, suggesting that KdmB has additional functions apart from histone demethylation. In this study, we identified demethylase-independent functions of KdmB in transcriptional regulation of SM gene clusters. Furthermore, we show that this activating and demethylase-independent role of the H3K4 demethylase is also conserved in the phytopathogenic fungus Fusarium graminearum. Lack of FgKdm5 resulted in significant downregulation of five of seven analyzed SMs, whereby only one SMGC depends on a functional JmjC-domain. In A. nidulans strains deficient in H3K4 methylation, i.e., cclA∆, largely phenocopied kdmB∆, while this is not the case for most of the SMs analyzed in Fusarium spp. Notably, KdmB could not rescue the demethylase function in ∆fgkdm5 but restored all demethylase-independent phenotypes.

Original languageEnglish
JournalFrontiers in Microbiology
Volume10
Pages (from-to)1759
ISSN1664-302X
DOIs
Publication statusPublished - 2019

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Histone Demethylases
Secondary Metabolism
Aspergillus nidulans
Fusarium
Multigene Family
Histones
Post Translational Protein Processing
Jumonji Domain-Containing Histone Demethylases
Fungi
Genes
Genetic Promoter Regions
Methylation
Lysine
Chromatin
Down-Regulation
Phenotype
Research

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title = "Evidence of a Demethylase-Independent Role for the H3K4-Specific Histone Demethylases in Aspergillus nidulans and Fusarium graminearum Secondary Metabolism",
abstract = "Fungi produce a plethora of secondary metabolites (SMs) involved in cellular protection, defense, and signaling. Like other metabolic processes, transcription of SM biosynthesis genes is tightly regulated to prevent an unnecessary use of resources. Genes involved in SM biosynthesis are usually physically linked, arranged in secondary metabolite gene clusters (SMGCs). Research over the last decades has shown that chromatin structure and posttranslational modifications (PTMs) of histones represent important layers of SMGC regulation. For instance, trimethylation of histone H3 lysine 4 (H3K4me3) is a PTM typically associated with promoter regions of actively transcribed genes. Previously, we have shown that the H3K4me3-specific, JmjC domain-containing histone demethylase KdmB functions not only in repression but also in activation of secondary metabolism in Aspergillus nidulans, suggesting that KdmB has additional functions apart from histone demethylation. In this study, we identified demethylase-independent functions of KdmB in transcriptional regulation of SM gene clusters. Furthermore, we show that this activating and demethylase-independent role of the H3K4 demethylase is also conserved in the phytopathogenic fungus Fusarium graminearum. Lack of FgKdm5 resulted in significant downregulation of five of seven analyzed SMs, whereby only one SMGC depends on a functional JmjC-domain. In A. nidulans strains deficient in H3K4 methylation, i.e., cclA∆, largely phenocopied kdmB∆, while this is not the case for most of the SMs analyzed in Fusarium spp. Notably, KdmB could not rescue the demethylase function in ∆fgkdm5 but restored all demethylase-independent phenotypes.",
author = "Simone Bachleitner and S{\o}rensen, {Jens Laurids} and Agnieszka Gacek-Matthews and Michael Sulyok and Lena Studt and Joseph Strauss",
year = "2019",
doi = "10.3389/fmicb.2019.01759",
language = "English",
volume = "10",
pages = "1759",
journal = "Frontiers in Microbiology",
issn = "1664-302X",
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Evidence of a Demethylase-Independent Role for the H3K4-Specific Histone Demethylases in Aspergillus nidulans and Fusarium graminearum Secondary Metabolism. / Bachleitner, Simone; Sørensen, Jens Laurids; Gacek-Matthews, Agnieszka; Sulyok, Michael; Studt, Lena; Strauss, Joseph.

In: Frontiers in Microbiology, Vol. 10, 2019, p. 1759.

Research output: Contribution to journalJournal articleResearchpeer-review

TY - JOUR

T1 - Evidence of a Demethylase-Independent Role for the H3K4-Specific Histone Demethylases in Aspergillus nidulans and Fusarium graminearum Secondary Metabolism

AU - Bachleitner, Simone

AU - Sørensen, Jens Laurids

AU - Gacek-Matthews, Agnieszka

AU - Sulyok, Michael

AU - Studt, Lena

AU - Strauss, Joseph

PY - 2019

Y1 - 2019

N2 - Fungi produce a plethora of secondary metabolites (SMs) involved in cellular protection, defense, and signaling. Like other metabolic processes, transcription of SM biosynthesis genes is tightly regulated to prevent an unnecessary use of resources. Genes involved in SM biosynthesis are usually physically linked, arranged in secondary metabolite gene clusters (SMGCs). Research over the last decades has shown that chromatin structure and posttranslational modifications (PTMs) of histones represent important layers of SMGC regulation. For instance, trimethylation of histone H3 lysine 4 (H3K4me3) is a PTM typically associated with promoter regions of actively transcribed genes. Previously, we have shown that the H3K4me3-specific, JmjC domain-containing histone demethylase KdmB functions not only in repression but also in activation of secondary metabolism in Aspergillus nidulans, suggesting that KdmB has additional functions apart from histone demethylation. In this study, we identified demethylase-independent functions of KdmB in transcriptional regulation of SM gene clusters. Furthermore, we show that this activating and demethylase-independent role of the H3K4 demethylase is also conserved in the phytopathogenic fungus Fusarium graminearum. Lack of FgKdm5 resulted in significant downregulation of five of seven analyzed SMs, whereby only one SMGC depends on a functional JmjC-domain. In A. nidulans strains deficient in H3K4 methylation, i.e., cclA∆, largely phenocopied kdmB∆, while this is not the case for most of the SMs analyzed in Fusarium spp. Notably, KdmB could not rescue the demethylase function in ∆fgkdm5 but restored all demethylase-independent phenotypes.

AB - Fungi produce a plethora of secondary metabolites (SMs) involved in cellular protection, defense, and signaling. Like other metabolic processes, transcription of SM biosynthesis genes is tightly regulated to prevent an unnecessary use of resources. Genes involved in SM biosynthesis are usually physically linked, arranged in secondary metabolite gene clusters (SMGCs). Research over the last decades has shown that chromatin structure and posttranslational modifications (PTMs) of histones represent important layers of SMGC regulation. For instance, trimethylation of histone H3 lysine 4 (H3K4me3) is a PTM typically associated with promoter regions of actively transcribed genes. Previously, we have shown that the H3K4me3-specific, JmjC domain-containing histone demethylase KdmB functions not only in repression but also in activation of secondary metabolism in Aspergillus nidulans, suggesting that KdmB has additional functions apart from histone demethylation. In this study, we identified demethylase-independent functions of KdmB in transcriptional regulation of SM gene clusters. Furthermore, we show that this activating and demethylase-independent role of the H3K4 demethylase is also conserved in the phytopathogenic fungus Fusarium graminearum. Lack of FgKdm5 resulted in significant downregulation of five of seven analyzed SMs, whereby only one SMGC depends on a functional JmjC-domain. In A. nidulans strains deficient in H3K4 methylation, i.e., cclA∆, largely phenocopied kdmB∆, while this is not the case for most of the SMs analyzed in Fusarium spp. Notably, KdmB could not rescue the demethylase function in ∆fgkdm5 but restored all demethylase-independent phenotypes.

U2 - 10.3389/fmicb.2019.01759

DO - 10.3389/fmicb.2019.01759

M3 - Journal article

VL - 10

SP - 1759

JO - Frontiers in Microbiology

JF - Frontiers in Microbiology

SN - 1664-302X

ER -