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The Fusarium graminearum Histone H3 K27 Methyltransferase KMT6 Regulates Development and Expression of Secondary Metabolite Gene Clusters

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Title The Fusarium graminearum Histone H3 K27 Methyltransferase KMT6 Regulates Development and Expression of Secondary Metabolite Gene Clusters
Names Connolly, Lanelle R. (creator)
Smith, Kristina M. (creator)
Freitag, Michael (creator)
Date Issued 2013-10-31 (iso8601)
Note This is the publisher’s final pdf. The published article is copyrighted by the author(s) and published by the Public Library of Science. The published article can be found at: http://www.plosgenetics.org/.
Abstract The cereal pathogen Fusarium graminearum produces secondary metabolites toxic to humans and animals, yet coordinated
transcriptional regulation of gene clusters remains largely a mystery. By chromatin immunoprecipitation and high-throughput
DNA sequencing (ChIP-seq) we found that regions with secondary metabolite clusters are enriched for
trimethylated histone H3 lysine 27 (H3K27me3), a histone modification associated with gene silencing. H3K27me3 was
found predominantly in regions that lack synteny with other Fusarium species, generally subtelomeric regions. Di- or
trimethylated H3K4 (H3K4me2/3), two modifications associated with gene activity, and H3K27me3 are predominantly found
in mutually exclusive regions of the genome. To find functions for H3K27me3, we deleted the gene for the putative H3K27
methyltransferase, KMT6, a homolog of Drosophila Enhancer of zeste, E(z). The kmt6 mutant lacks H3K27me3, as shown by
western blot and ChIP-seq, displays growth defects, is sterile, and constitutively expresses genes for mycotoxins, pigments
and other secondary metabolites. Transcriptome analyses showed that 75% of 4,449 silent genes are enriched for
H3K27me3. A subset of genes that were enriched for H3K27me3 in WT gained H3K4me2/3 in kmt6. A largely overlapping set
of genes showed increased expression in kmt6. Almost 95% of the remaining 2,720 annotated silent genes showed no
enrichment for either H3K27me3 or H3K4me2/3 in kmt6. In these cases mere absence of H3K27me3 was insufficient for
expression, which suggests that additional changes are required to activate genes. Taken together, we show that absence
of H3K27me3 allowed expression of an additional 14% of the genome, resulting in derepression of genes predominantly
involved in secondary metabolite pathways and other species-specific functions, including putative secreted pathogenicity
factors. Results from this study provide the framework for novel targeted strategies to control the ‘‘cryptic genome’’,
specifically secondary metabolite expression.
Genre Article
Access Condition http://creativecommons.org/licenses/by/3.0/us/
Identifier Connolly LR, Smith KM, Freitag M (2013) The Fusarium graminearum Histone H3 K27 Methyltransferase KMT6 Regulates Development and Expression of Secondary Metabolite Gene Clusters. PLoS Genetics 9(10): e1003916. doi:10.1371/journal.pgen.1003916

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