Academic journal article Genetics

The Histone Acetyltransferase GcnE (GCN5) Plays a Central Role in the Regulation of Aspergillus Asexual Development

Academic journal article Genetics

The Histone Acetyltransferase GcnE (GCN5) Plays a Central Role in the Regulation of Aspergillus Asexual Development

Article excerpt

CHROMATIN rearrangements are associated with the transcriptional regulation of gene expression in eukaryotes. For example, facultative heterochromatin can be associated with the transcriptionally active or silent states of developmentally regulated loci (Grewal and Jia 2007). This is achieved in part through histone post translational modifications (PTM), which play a very important role in the control of these active or silent chromatin states. Histone modifications include acetylation, methylation, phosphorylation, and ubiquitination at different positions of the histone proteins. In particular, acetylation of lysine 9 or lysine 14 in histone H3 has been associated with activation of transcription. Acetylation of histones plays two roles in the regulation of transcription: it alters the physical properties of the histone-DNA interaction, and it also provides a frame for the binding of bromodomain proteins that remodel the chromatin and regulate gene expression (Spedale et al. 2012). These modifications regulate the nucleosome positioning at the gene promoters and the recruitment of the regulatory proteins. One of these modifiers, the SAGA complex, is responsible for the acetylation of several lysine residues in the N-terminal region of histones, particularly histone H3 lysine 9 (H3K9) and histone H3 lysine 14 (H3K14) (Kuo et al. 1996). The SAGA complex is a multimeric protein association with several subunits including Ada2p, Ada3p, Spt3p, and Tra1p (Grant et al. 1997; Spedale et al. 2012), where Gcn5p is the subunit with the histone acetyltransferase (HAT) catalytic activity (Grant et al. 1997). The SAGA complex is implicated in several functions related to transcription, such as transcription initiation and elongation, histone ubiquitination, and interactions of TATA-binding proteins. In addition, SAGA has also been implicated in messenger RNA (mRNA) export in yeasts and Drosophila (Rodriguez-Navarro et al. 2004; Kurshakova et al. 2007). In Saccharomyces cerevisiae, the SAGA complex is involved in the transcriptional regulation of 12% of the yeast genome. Approximately, a third of that 12% of the yeast genome is downregulated and two-thirds are upregulated in DGCN5 cells (Lee et al. 2000), implying a direct or indirect negative role of Gcn5p. Interestingly, a high proportion of genes regulated by SAGA are upregulated during the responses to environmental stresses (such as heat, oxidation, and starvation) (Huisinga and Pugh 2004). The SAGA complex is also present in metazoans, where it has diverged and evolved into four different complexes (two SAGA and two ATAC complexes), while lower eukaryotes, such as yeasts and other fungi, contain one single SAGA complex. It was hypothesized that this evolution into a diverse set of complexes is involved in cellular specialization during development and homeostasis in metazoans (Spedale et al. 2012). The SAGA and ATAC complexes participate in the regulation of genes in response to intracellular and extracellular signals: protein kinase C signaling, response to osmotic stress, UV-induced DNA damage, arsenite-induced signaling, endoplasmic reticulum stress, and nuclear receptor signaling (Spedale et al. 2012). Likewise, plants also have multiple HATs. In Arabidopsis, AtGCN5 is involved in many developmental processes (Servet et al. 2010).

Although elegant experimental approaches using Neurospora crassa as a model system have significantly contributed to general concepts of DNA methylation, genome defense, and heterochromatin formation (Tamaru and Selker 2001; Freitag et al. 2002, 2004; Honda et al. 2010; Rountree and Selker 2010), studies on transcriptionally related chromatin rearrangements and histone modifications are still scarce in filamentous fungi, a broad group of ecologically, industrially, and clinically important organisms. In N. crassa, the transcriptional activation of the light-inducible gene al-3 requires the acetylation of histone H3K14 by a homolog of Gcn5p, NGF-1 (Grimaldi et al. …

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