title: Overexpression of the Aspergillus nidulans histone 4 acetyltransferase EsaA increases activation of secondary metabolite production.
abstract: Regulation of secondary metabolite (SM) gene clusters in Aspergillus nidulans has been shown to occur through cluster-specific transcription factors or through global regulators of chromatin structure such as histone methyltransferases, histone deacetylases, or the putative methyltransferase LaeA. A multicopy suppressor screen for genes capable of returning SM production to the SM deficient ΔlaeA mutant resulted in identification of the essential histone acetyltransferase EsaA, able to complement an esa1 deletion in Saccharomyces cereviseae. Here we report that EsaA plays a novel role in SM cluster activation through histone 4 lysine 12 (H4K12) acetylation in four examined SM gene clusters (sterigmatocystin, penicillin, terrequinone and orsellinic acid), in contrast to no increase in H4K12 acetylation of the housekeeping tubA promoter. This augmented SM cluster acetylation requires LaeA for full effect and correlates with both increased transcript levels and metabolite production relative to wild type. H4K12 levels may thus represent a unique indicator of relative production potential, notably of SMs.
authors.affiliation: Department of Genetics, University of Wisconsin-Madison, 1550 Linden Drive, Madison, WI 53706, USA.
authors.forename: Alexandra A
authors.initials: AA
authors.lastname: Soukup
authors.forename: Yi-Ming
authors.initials: YM
authors.lastname: Chiang
authors.forename: Jin Woo
authors.initials: JW
authors.lastname: Bok
authors.forename: Yazmid
authors.initials: Y
authors.lastname: Reyes-Dominguez
authors.forename: Berl R
authors.initials: BR
authors.lastname: Oakley
authors.forename: Clay C C
authors.initials: CC
authors.lastname: Wang
authors.forename: Joseph
authors.initials: J
authors.lastname: Strauss
authors.forename: Nancy P
authors.initials: NP
authors.lastname: Keller
mesh_terms: D000107:Acetylation; D020816:Amino Acid Motifs; D001233:Aspergillus nidulans / Q000737:chemistry / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression; D015966:Gene Expression Regulation, Fungal; D051548:Histone Acetyltransferases / Q000235:genetics / Q000378:metabolism*; D006657:Histones / Q000737:chemistry / Q000378:metabolism*
chemical_list: D005656:Fungal Proteins; D006657:Histones; D051548:Histone Acetyltransferases