The complex Tup1‐Cyc8 bridges transcription factor ClrB and putative histone methyltransferase LaeA to activate the expression of cellulolytic genes

Abstract

The degradation of lignocellulosic biomass by cellulolytic enzymes is involved in the global carbon cycle. The hydrolysis of lignocellulosic biomass into fermentable sugars is potential as an excellent industrial resource to produce a variety of chemical products. The production of cellulolytic enzymes is regulated mainly at the transcriptional level in filamentous fungi. Transcription factor ClrB and the putative histone methyltransferase LaeA, are both necessary for the expression of cellulolytic genes. However, the mechanism by which transcription factors and methyltransferase coordinately regulate cellulolytic genes is still unknown. Here, we reveal a transcriptional regulatory mechanism involving Penicillium oxalicum transcription factor ClrB (PoClrB), complex Tup1‐Cyc8, and putative histone methyltransferase LaeA (PoLaeA). As the transcription factor, PoClrB binds the targeted promoters of cellulolytic genes, recruits PoTup1‐Cyc8 complex via direct interaction with PoTup1. PoTup1 interacts with PoCyc8 to form the coactivator complex PoTup1‐Cyc8. Then, PoTup1 recruits putative histone methyltransferase PoLaeA to modify the chromatin structure of the upstream region of cellulolytic genes, thereby facilitating the binding of transcription machinery to activating the corresponding cellulolytic gene expression. Our results contribute to a better understanding of complex transcriptional regulation mechanisms of cellulolytic genes and will be valuable for lignocellulosic biorefining.

The putative methyltransferase LaeA regulates mycelium growth and cellulase production in Myceliophthora thermophila

“…In contrast to RNA-seq data at day 2, ∆laeA showed increased expression of genes encoding CAZymes, including 46 GHs, 11 GT, 7 CBMs, two cellobiose dehydrogenases (AA8), and 11 LMPOs (AA9) as compared to WT, when cultured on cellulose for 4 d (Fig. 6c, Additional file 1: Tables S11, S12), which was not observed in T. reesei and P. oxalicum [16,21,22]. A Funcat analysis indicated that the set of 920 up-regulated genes was significantly enriched in the functional categories of C-compound and carbohydrate metabolism, fermentation, cellular import and two-component signal transduction system (sensor kinase component).…”

“…Previous reports suggested that LaeA has been linked to changes in chromatin structure in Apergillus [22,26,60] and regulation of gene transcription through lysine or arginine methylation of histones [16,17,[23][24][25].…”

“…It was reported that Lae1, the LaeA ortholog, modulates cellulase gene expression in T. reesei, a process dependent on the function of the general cellulase regulator XYR1 [16,20]. Similarly, in P. oxalicum, LaeA is necessary for the expression of cellulase activated by ClrB (an ortholog of Clr-2) [21,22]. Although LaeA played so important role in fungal growth and cellulase production, the mechanism of LaeA remains largely unclear.…”

“…In Aspergillus kawachii, LaeA controls the expression of CexA (citrate export protein) by adjusting the euchromatin/heterochromatin ratio of the cexA promoter region, thereby affecting the production of citric acid [26]. In addition, in cellulolytic fungus, its ortholog Lae1 regulates the expression of polysaccharide hydrolytic enzymes by modifying the chromatin structure of promoter regions of cellulolytic genes [22]. Similarly, A. nidulans LaeA was considered to remodel histone methylation levels to regulate expression of secondary metabolism genes [14].…”

The BcLAE1 is involved in the regulation of ABA biosynthesis in Botrytis cinerea TB-31

“… Patananan et al (2013) used [3H] AdoMet in Aspergillus nidulans to observe the automethylation of LaeA only on methionine residues, but there was more and more evidence that LAE1 was involved in histone modification. In Penicillium oxalicum , PoTup1 recruited methyltransferase PoLaeA to modify the chromatin structure of the upstream region of the cellulose decomposition gene, thereby promoting the binding of transcription mechanisms to activate the corresponding cellulose gene expression ( Zhang et al, 2022 ). In Trichoderma reesei , LAE1 induces gene expression by changing the H3K4me3 marks ( Karimi-Aghcheh et al, 2013 ).…”