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

2.50
Hdl Handle:
http://hdl.handle.net/10033/620522
Title:
KdmB, a Jumonji Histone H3 Demethylase, Regulates Genome-Wide H3K4 Trimethylation and Is Required for Normal Induction of Secondary Metabolism in Aspergillus nidulans.
Authors:
Gacek-Matthews, Agnieszka; Berger, Harald; Sasaki, Takahiko; Wittstein, Kathrin; Gruber, Clemens; Lewis, Zachary A; Strauss, Joseph
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.
Affiliation:
Helmholtzzentrum für Infektionsforschung, Inhoffenstrasse 7, 38124 Braunschweig
Citation:
KdmB, a Jumonji Histone H3 Demethylase, Regulates Genome-Wide H3K4 Trimethylation and Is Required for Normal Induction of Secondary Metabolism in Aspergillus nidulans. 2016, 12 (8):e1006222 PLoS Genet.
Journal:
PLoS genetics
Issue Date:
Aug-2016
URI:
http://hdl.handle.net/10033/620522
DOI:
10.1371/journal.pgen.1006222
PubMed ID:
27548260
Type:
Article
Language:
en
ISSN:
1553-7404
Appears in Collections:
publications of the department of microbial drugs (MWIS)

Full metadata record

DC FieldValue Language
dc.contributor.authorGacek-Matthews, Agnieszkaen
dc.contributor.authorBerger, Haralden
dc.contributor.authorSasaki, Takahikoen
dc.contributor.authorWittstein, Kathrinen
dc.contributor.authorGruber, Clemensen
dc.contributor.authorLewis, Zachary Aen
dc.contributor.authorStrauss, Josephen
dc.date.accessioned2016-09-22T09:58:44Z-
dc.date.available2016-09-22T09:58:44Z-
dc.date.issued2016-08-
dc.identifier.citationKdmB, a Jumonji Histone H3 Demethylase, Regulates Genome-Wide H3K4 Trimethylation and Is Required for Normal Induction of Secondary Metabolism in Aspergillus nidulans. 2016, 12 (8):e1006222 PLoS Genet.en
dc.identifier.issn1553-7404-
dc.identifier.pmid27548260-
dc.identifier.doi10.1371/journal.pgen.1006222-
dc.identifier.urihttp://hdl.handle.net/10033/620522-
dc.description.abstractHistone 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.en
dc.language.isoenen
dc.rightsopenAccessen
dc.titleKdmB, a Jumonji Histone H3 Demethylase, Regulates Genome-Wide H3K4 Trimethylation and Is Required for Normal Induction of Secondary Metabolism in Aspergillus nidulans.en
dc.typeArticleen
dc.contributor.departmentHelmholtzzentrum für Infektionsforschung, Inhoffenstrasse 7, 38124 Braunschweigen
dc.identifier.journalPLoS geneticsen

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