Membrane-Bound Methyltransferase Complex VapA-VipC-VapB Guides Epigenetic Control of Fungal Development

Abstract

Epigenetic and transcriptional control of gene expression must be coordinated in response to external signals to promote alternative multicellular developmental programs. The membrane-associated trimeric complex VapA-VipC-VapB controls a signal transduction pathway for fungal differentiation. The VipC-VapB methyltransferases are tethered to the membrane by the FYVE-like zinc finger protein VapA, allowing the nuclear VelB-VeA-LaeA complex to activate transcription for sexual development. Once the release from VapA is triggered, VipC-VapB is transported into the nucleus. VipC-VapB physically interacts with VeA and reduces its nuclear import and protein stability, thereby reducing the nuclear VelB-VeA-LaeA complex. Nuclear VapB methyltransferase diminishes the establishment of facultative heterochromatin by decreasing histone 3 lysine 9 trimethylation (H3K9me3). This favors activation of the regulatory genes brlA and abaA, which promote the asexual program. The VapA-VipC-VapB methyltransferase pathway combines control of nuclear import and stability of transcription factors with histone modification to foster appropriate differentiation responses.

The VELVET A Orthologue VEL1 of Trichoderma reesei Regulates Fungal Development and Is Essential for Cellulase Gene Expression

“…Most studies on veA have been carried out in Aspergillus spp., where this gene has been described to control photodependent development, secondary metabolism and pathogenesis-associated processes [14]–[16]. Thorough genetic, molecular, and biochemical work has recently shown that Velvet is part of a high-molecular-weight complex containing at least 10 different proteins, some of which have been assigned distinct regulatory roles [15], [22]–[26]. The VeA orthologue VEL1 of Trichoderma virens has been shown to regulate sporulation, chlamydospore formation, secondary metabolite synthesis and mycoparasitism [27].…”

Fungal Morphogenesis, from the Polarized Growth of Hyphae to Complex Reproduction and Infection Structures

“…Release to the nucleus depends on environmental conditions where asexual development is favored. Nuclear VipC-VapB reduces negative histone tags and promotes asexual development (377).…”

Genome-Wide Chromatin Immunoprecipitation Sequencing Analysis of the Penicillium chrysogenum Velvet Protein PcVelA Identifies Methyltransferase PcLlmA as a Novel Downstream Regulator of Fungal Development

“…Because recent reports from other euascomycetes point to a functional link between VeA homologs and several putative MTases (40 – 42), we focused further analyses on this group of new PcVelA target genes. First, we performed quantitative reverse transcription-PCR (qRT-PCR) analysis to validate the PcVelA-dependent expression of MTase-encoding genes.…”

“…Pc18g06010 showed PcVelA-dependent expression in qRT-PCR but not in microarray analysis (Table 2). Next, the amino acid sequences of the putative MTases were compared to the sequences of PcLaeA, a putative methyltransferase that is part of the velvet complex, as well as A. nidulans LlmF, VapB, and VipC (homolog of PcLlmB), which have previously been described as velvet-associated proteins (40, 41). In general, a set of three conserved sequence motifs (motifs I to III) that are essential for catalytic activity are found in most MTases (43, 44).…”

“…In general, a set of three conserved sequence motifs (motifs I to III) that are essential for catalytic activity are found in most MTases (43, 44). The most prominent one, motif I, is characterized by the glycine (G)-rich sequence E/DXGXGXG, which is conserved in fungi, plants, and humans (41, 45, 46). Overall comparison of amino acid sequences revealed that PcLlmA, PcLlmB, and PcLaeA, as well as LlmF, VapB, and VipC from A. nidulans , had only moderate similarity (Fig.…”