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PMID: 20132440 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, U.S. Gov't, Non-P.H.S.

Heterochromatic marks are associated with the repression of secondary metabolism clusters in Aspergillus nidulans.

Molecular microbiology ·Vol. 76 ·No. 6 ·2010-06-00 ·Pages 1376-86

Reyes-Dominguez Y, Bok JW, Berger H, Shwab EK, Basheer A, Gallmetzer A, Scazzocchio C, Keller N, Strauss J

Abstract

Fungal secondary metabolites are important bioactive compounds but the conditions leading to expression of most of the putative secondary metabolism (SM) genes predicted by fungal genomics are unknown. Here we describe a novel mechanism involved in SM-gene regulation based on the finding that, in Aspergillus nidulans, mutants lacking components involved in heterochromatin formation show de-repression of genes involved in biosynthesis of sterigmatocystin (ST), penicillin and terrequinone A. During the active growth phase, the silent ST gene cluster is marked by histone H3 lysine 9 trimethylation and contains high levels of the heterochromatin protein-1 (HepA). Upon growth arrest and activation of SM, HepA and trimethylated H3K9 levels decrease concomitantly with increasing levels of acetylated histone H3. SM-specific chromatin modifications are restricted to genes located inside the ST cluster, and constitutive heterochromatic marks persist at loci immediately outside the cluster. LaeA, a global activator of SM clusters in fungi, counteracts the establishment of heterochromatic marks. Thus, one level of regulation of the A. nidulans ST cluster employs epigenetic control by H3K9 methylation and HepA binding to establish a repressive chromatin structure and LaeA is involved in reversal of this heterochromatic signature inside the cluster, but not in that of flanking genes.

MeSH Terms
Acetylation Aspergillus nidulans/genetics,metabolism Fungal Proteins/biosynthesis Gene Expression Regulation, Fungal Heterochromatin/metabolism Histones/metabolism Indoles/metabolism Methylation Multigene Family Penicillins/metabolism Sterigmatocystin/metabolism
Chemicals
Fungal Proteins Heterochromatin Histones Indoles Penicillins terrequinone A Sterigmatocystin
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Reyes-Dominguez Yazmid
Fungal Genetics and Genomics Unit, Austrian Institute of Technology (AIT) and University of Natural Resources and Applied Life Sciences (BOKU) Vienna, Austria.
Bok Jin Woo
Berger Harald
Shwab E Keats
Basheer Asjad
Gallmetzer Andreas
Scazzocchio Claudio
Keller Nancy
Strauss Joseph
References (54)
54 references, click to expand
  1. Heterochromatin protein 1: a pervasive controlling influence.
    Cell Mol Life Sci. 2005 Dec;62(23):2711-26 PMID: 16261261
  2. Natural products of filamentous fungi: enzymes, genes, and their regulation.
    Nat Prod Rep. 2007 Apr;24(2):393-416 PMID: 17390002
  3. Nuclear export of the transcription factor NirA is a regulatory checkpoint for nitrate induction in Aspergillus nidulans.
    Mol Cell Biol. 2007 Feb;27(3):791-802 PMID: 17116695
  4. Functional and physical interaction between the histone methyl transferase Suv39H1 and histone deacetylases.
    Nucleic Acids Res. 2002 Jan 15;30(2):475-81 PMID: 11788710
  5. LaeA, a regulator of secondary metabolism in Aspergillus spp.
    Eukaryot Cell. 2004 Apr;3(2):527-35 PMID: 15075281
  6. The genetics of Aspergillus nidulans.
    Adv Genet. 1953;5:141-238 PMID: 13040135
  7. HP1: a functionally multifaceted protein.
    Curr Opin Genet Dev. 2008 Apr;18(2):169-74 PMID: 18329871
  8. Requirement of LaeA for secondary metabolism and sclerotial production in Aspergillus flavus.
    Fungal Genet Biol. 2008 Oct;45(10):1422-9 PMID: 18667168
  9. The chromodomain protein Swi6: a key component at fission yeast centromeres.
    Science. 1995 Sep 8;269(5229):1429-31 PMID: 7660126
  10. The role of chromatin during transcription.
    Cell. 2007 Feb 23;128(4):707-19 PMID: 17320508
  11. Secondary metabolic gene cluster silencing in Aspergillus nidulans.
    Mol Microbiol. 2006 Sep;61(6):1636-45 PMID: 16968230
  12. The GATA factor AreA is essential for chromatin remodelling in a eukaryotic bidirectional promoter.
    EMBO J. 1999 Mar 15;18(6):1584-97 PMID: 10075929
  13. The initiation and pattern of spread of histone H4 acetylation parallel the order of transcriptional activation of genes in the aflatoxin cluster.
    Mol Microbiol. 2007 Nov;66(3):713-26 PMID: 17919289
  14. veA is required for toxin and sclerotial production in Aspergillus parasiticus.
    Appl Environ Microbiol. 2004 Aug;70(8):4733-9 PMID: 15294809
  15. Reversible disruption of pericentric heterochromatin and centromere function by inhibiting deacetylases.
    Nat Cell Biol. 2001 Feb;3(2):114-20 PMID: 11175742
  16. The requirements for COMPASS and Paf1 in transcriptional silencing and methylation of histone H3 in Saccharomyces cerevisiae.
    Genetics. 2006 Jun;173(2):557-67 PMID: 16582434
  17. Role of histone H3 lysine 9 methylation in epigenetic control of heterochromatin assembly.
    Science. 2001 Apr 6;292(5514):110-3 PMID: 11283354
  18. Heterochromatin protein 1: don't judge the book by its cover!
    Curr Opin Genet Dev. 2006 Apr;16(2):143-50 PMID: 16503133
  19. Fungal secondary metabolism - from biochemistry to genomics.
    Nat Rev Microbiol. 2005 Dec;3(12):937-47 PMID: 16322742
  20. Physical and functional association of SU(VAR)3-9 and HDAC1 in Drosophila.
    EMBO Rep. 2001 Oct;2(10):915-9 PMID: 11571273
  21. Genomic mining for Aspergillus natural products.
    Chem Biol. 2006 Jan;13(1):31-7 PMID: 16426969
  22. Natural history of S-adenosylmethionine-binding proteins.
    BMC Struct Biol. 2005 Oct 14;5:19 PMID: 16225687
  23. The heterochromatin protein 1 prevents telomere fusions in Drosophila.
    Mol Cell. 1998 Nov;2(5):527-38 PMID: 9844626
  24. Self-interaction of heterochromatin protein 1 is required for direct binding to histone methyltransferase, SUV39H1.
    Biochem Biophys Res Commun. 2003 Feb 7;301(2):287-92 PMID: 12565857
  25. Histone deacetylase activity regulates chemical diversity in Aspergillus.
    Eukaryot Cell. 2007 Sep;6(9):1656-64 PMID: 17616629
  26. Mutations in the fission yeast silencing factors clr4+ and rik1+ disrupt the localisation of the chromo domain protein Swi6p and impair centromere function.
    J Cell Sci. 1996 Nov;109 ( Pt 11):2637-48 PMID: 8937982
  27. Chromatin-level regulation of biosynthetic gene clusters.
    Nat Chem Biol. 2009 Jul;5(7):462-4 PMID: 19448638
  28. VelB/VeA/LaeA complex coordinates light signal with fungal development and secondary metabolism.
    Science. 2008 Jun 13;320(5882):1504-6 PMID: 18556559
  29. Relationship between secondary metabolism and fungal development.
    Microbiol Mol Biol Rev. 2002 Sep;66(3):447-59, table of contents PMID: 12208999
  30. Transitions in distinct histone H3 methylation patterns at the heterochromatin domain boundaries.
    Science. 2001 Aug 10;293(5532):1150-5 PMID: 11498594
  31. LaeA, a regulator of morphogenetic fungal virulence factors.
    Eukaryot Cell. 2005 Sep;4(9):1574-82 PMID: 16151250
  32. Heterochromatin protein 1 is required for correct chromosome segregation in Drosophila embryos.
    J Cell Sci. 1995 Apr;108 ( Pt 4):1419-31 PMID: 7615663
  33. HP1 is essential for DNA methylation in neurospora.
    Mol Cell. 2004 Feb 13;13(3):427-34 PMID: 14967149
  34. Regulation of chromatin structure by site-specific histone H3 methyltransferases.
    Nature. 2000 Aug 10;406(6796):593-9 PMID: 10949293
  35. Chemical induction of silent biosynthetic pathway transcription in Aspergillus niger.
    J Ind Microbiol Biotechnol. 2009 Sep;36(9):1199-213 PMID: 19521728
  36. Metabolic Pathway Gene Clusters in Filamentous Fungi
    Fungal Genet Biol. 1997 Feb;21(1):17-29 PMID: 9073477
  37. Characterization of sequences associated with position-effect variegation at pericentric sites in Drosophila heterochromatin.
    Chromosoma. 1998 Nov;107(5):277-85 PMID: 9880760
  38. Transformation by integration in Aspergillus nidulans.
    Gene. 1983 Dec;26(2-3):205-21 PMID: 6368319
  39. Conservation of heterochromatin protein 1 function.
    Mol Cell Biol. 2000 Sep;20(18):6970-83 PMID: 10958692
  40. The global regulator LaeA controls penicillin biosynthesis, pigmentation and sporulation, but not roquefortine C synthesis in Penicillium chrysogenum.
    Biochimie. 2009 Feb;91(2):214-25 PMID: 18952140
  41. Epigenetic remodeling of the fungal secondary metabolome.
    Org Biomol Chem. 2008 Jun 7;6(11):1895-7 PMID: 18480899
  42. Mutations derepressing silent centromeric domains in fission yeast disrupt chromosome segregation.
    Genes Dev. 1995 Jan 15;9(2):218-33 PMID: 7851795
  43. Chromosomal location plays a role in regulation of aflatoxin gene expression in Aspergillus parasiticus.
    Appl Environ Microbiol. 2002 Jan;68(1):306-15 PMID: 11772640
  44. Structure and activity of enzymes that remove histone modifications.
    Curr Opin Struct Biol. 2005 Dec;15(6):673-80 PMID: 16263263
  45. Relics of repeat-induced point mutation direct heterochromatin formation in Neurospora crassa.
    Genome Res. 2009 Mar;19(3):427-37 PMID: 19092133
  46. Functional mammalian homologues of the Drosophila PEV-modifier Su(var)3-9 encode centromere-associated proteins which complex with the heterochromatin component M31.
    EMBO J. 1999 Apr 1;18(7):1923-38 PMID: 10202156
  47. Silencing of the aflatoxin gene cluster in a diploid strain of Aspergillus flavus is suppressed by ectopic aflR expression.
    Genetics. 2007 Aug;176(4):2077-86 PMID: 17565943
  48. Double-joint PCR: a PCR-based molecular tool for gene manipulations in filamentous fungi.
    Fungal Genet Biol. 2004 Nov;41(11):973-81 PMID: 15465386
  49. Regulation of secondary metabolism in filamentous fungi.
    Annu Rev Phytopathol. 2005;43:437-58 PMID: 16078891
  50. Trimethylated lysine 9 of histone H3 is a mark for DNA methylation in Neurospora crassa.
    Nat Genet. 2003 May;34(1):75-9 PMID: 12679815
  51. H3K9 methylation regulates growth and development in Aspergillus fumigatus.
    Eukaryot Cell. 2008 Dec;7(12):2052-60 PMID: 18849468
  52. HP1 controls telomere capping, telomere elongation, and telomere silencing by two different mechanisms in Drosophila.
    Mol Cell. 2004 Aug 13;15(3):467-76 PMID: 15304225
  53. Dissecting individual steps of nitrogen transcription factor cooperation in the Aspergillus nidulans nitrate cluster.
    Mol Microbiol. 2008 Sep;69(6):1385-98 PMID: 18673441
  54. Transcriptional regulation of chemical diversity in Aspergillus fumigatus by LaeA.
    PLoS Pathog. 2007 Apr;3(4):e50 PMID: 17432932
Article Info
Journal
Molecular microbiology
Abbr.
Mol Microbiol
ISSN
1365-2958
Published
2010-06-00
Epub
2010-00-01
Pages
1376-86
Language
English
Region
England
NLM ID
8712028
PMCID
PMC2904488
Subset
IM
Grants
PHS HHS · 1 R01 AL065728-01 · United States
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