Cited by 122Genomics and Chromatin DynamicsMicrobial Natural Products and BiosynthesisFungal and yeast genetics research

KdmB, a Jumonji Histone H3 Demethylase, Regulates Genome-Wide H3K4 Trimethylation and Is Required for Normal Induction of Secondary Metabolism in Aspergillus nidulans

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Gacek-Matthews, Agnieszka, Berger, Harald, Sasaki, Takahiko, Wittstein, Kathrin, Gruber, Clemens, Lewis, Zachary A., Strauss, Joseph·2016·PLOS Genetics

Abstract

Histone posttranslational modifications (HPTMs) are involved in chromatin-based regulation of fungal secondary metabolite biosynthesis (SMB) in which the corresponding genes-usually physically linked in co-regulated clusters-are silenced under optimal physiological conditions (nutrient-rich) but are activated when nutrients are limiting. The exact molecular mechanisms by which HPTMs influence silencing and activation, however, are still to be better understood. Here we show by a combined approach of quantitative mass spectrometry (LC-MS/MS), genome-wide chromatin immunoprecipitation (ChIP-seq) and transcriptional network analysis (RNA-seq) that the core regions of silent A. nidulans SM clusters generally carry low levels of all tested chromatin modifications and that heterochromatic marks flank most of these SM clusters. During secondary metabolism, histone marks typically associated with transcriptional activity such as H3 trimethylated at lysine-4 (H3K4me3) are established in some, but not all gene clusters even upon full activation. KdmB, a Jarid1-family histone H3 lysine demethylase predicted to comprise a BRIGHT domain, a zinc-finger and two PHD domains in addition to the catalytic Jumonji domain, targets and demethylates H3K4me3 in vivo and mediates transcriptional downregulation. Deletion of kdmB leads to increased transcription of about ~1750 genes across nutrient-rich (primary metabolism) and nutrient-limiting (secondary metabolism) conditions. Unexpectedly, an equally high number of genes exhibited reduced expression in the kdmB deletion strain and notably, this group was significantly enriched for genes with known or predicted functions in secondary metabolite biosynthesis. Taken together, this study extends our general knowledge about multi-domain KDM5 histone demethylases and provides new details on the chromatin-level regulation of fungal secondary metabolite production.

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Crossref · 10.1371/journal.pgen.1006222

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  • Several genes were assigned to clusters enriched for gene sets consistent with their known functions, including KDM1B, BRSK2, and ITSN1, consistent with published functional evidence.

    “Several genes were assigned to clusters that showed enrichment for gene sets consistent with their known functions, including KDM1B,41 BRSK2,42 and ITSN143 consistent with published functional evidence”

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  1. [39]Gacek-Matthews A., Noble L.M., Gruber C., Berger H., Sulyok M., Marcos A.T, et al KdmA, a histone H3 demethylase with bipartite function, differentially regulates primary and secondary metabolism in Aspergillus nidulans. Molecular microbiology. accepted with minor revision. PMC4949671 25712266
  2. [40]Gacek-Matthews A, Noble LM, Gruber C, Berger H, Sulyok M, Marcos AT, et al KdmA, a histone H3 demethylase with bipartite function, differentially regulates primary and secondary metabolism in Aspergillus nidulans. Mol Microbiol. 2015. PMC4949671 25712266

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Authors
Gacek-Matthews, A., Berger, H., Sasaki, T., Wittstein, K., Gruber, C., Lewis, Z. A., & Strauss, J.
Affiliations
  • AIT Austrian Institute of Technology GmbH (AT)
  • University of Georgia (US)
  • Helmholtz Centre for Infection Research (DE)
Corresponding author
Strauss, Joseph
Venue
PLOS Genetics
Published
2016-08-22
Volume
12
Issue
8
Pages
e1006222
ISSN
  • 1553-7390 (ISSN-L)
  • 1553-7404
OpenAlex
W2512239244
Cited by
105
References
111
Citations by year
2026: 6 · 2025: 5 · 2024: 10 · 2023: 9 · 2022: 16 · 2021: 19 · 2020: 15 · 2019: 9 · 2018: 7 · 2017: 9
FWCI
4.33
Type
journal article
Language
en
Open access
Locations
  • PLoS Genetics (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • HZI (Helmholtz Centre for Infection Research) (submittedVersion, other-oa)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Figshare (submittedVersion, cc-by)
Funders
  • Austrian Science Fund (F3703)
  • Lower Austria Science Fund NFB (LS12-009)
  • American Cancer Society (RSG-14-184-01-DMC.)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
  • Health Sciences › Medicine › Pharmacology › Microbial Natural Products and Biosynthesis
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
Keywords
H3K4 trimethylation, histone demethylation, Aspergillus nidulans, fungal secondary metabolism, secondary metabolite gene clusters, chromatin regulation, nutrient limitation, transcriptional downregulation, heterochromatin, gene silencing
MeSH terms
Aspergillus nidulans, Chromatin, Histones, Humans, Gene Expression Regulation, Fungal, Genome, DNA Methylation, Tandem Mass Spectrometry, Histone Demethylases, Jumonji Domain-Containing Histone Demethylases, Secondary Metabolism

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