MURAL - Maynooth University Research Archive Library



    Molecular Functions of Histone Demethylase MERCK complex on Fungal Development and Secondary Metabolism in Filamentous Fungus Aspergillus nidulans and Aspergillus flavus


    Ulas, Mevlut (2018) Molecular Functions of Histone Demethylase MERCK complex on Fungal Development and Secondary Metabolism in Filamentous Fungus Aspergillus nidulans and Aspergillus flavus. PhD thesis, National University of Ireland Maynooth.

    Abstract

    Fungi has ability to produce a wide range of natural products called secondary metabolites. The production of these metabolites is tightly related with fungal development. SMproduction and development were shown to be affected by environmental factors such as light, pH and CO> level. Many of studies reported that regulation of these two processes is carried out by regulatory heteromeric protein complexes. SMproduction has been also shown to be associated with post-translational modifications in A.nidulans. Recently reported histone demethylase KdmA effects development and SM mechanisms in A. nidulans. This research study demonstrates molecular role ofKdmA as well as its interacting proteins inA.nidulans and plant pathogen A.jlavus. Comparative affinity purification coupled-MS analysis of KdmA showed that it phiscally interacts with four proteins MemA, EcmB, RstB, CclA and lead to form a complex(MERCK). Complex formation was also confirmed by performing MS-based analysis of other members by using different tags TAP, GFP, HA and MYC inA.nidulans andA.jlavus. Morphology analysis revealed that deletion of cclA and ecmB cause significant decrease on sexual and asexual growth structures production as well as colony size in A. nidulans and A.jlavus. Individual single and double deletion mutants of complex members exhibited significant alterations on production of secondary metabolites in both organisms. In addition, subcellular localization of complex members was investigated by using laser confocal microscopy and they were found to be localized in the nucleus. MS-based analysis showed no physical interaction between complex members in the absence of KdmA in A. nidulans. Genome-wide binding analysis (ChIP-seq) of complex members indicated common targets on the genome in A. nidulans supporting the effects on development and SM production and complex formation analysis data. Further active gene expression analysis (RNA pol II ChIPseq) of complex members presented downregulation of SM and fungal development related genes in A. nidulans particularly repressor role of CclA on SM. It was also found that KdmA and CclA play a critical role on PTMs. H3K4me3, H3K9me3 and H3K36me3 mark signals significantly influenced in the absence of cclA in A. nidulans. Overall, this study highlights molecular function of MERCK complex by facilitating molecular genetics and biochemical approaches.
    Item Type: Thesis (PhD)
    Keywords: Molecular Functions; Histone Demethylase MERCK complex; Fungal Development; Secondary Metabolism; Filamentous Fungus; Aspergillus nidulans; Aspergillus flavus;
    Academic Unit: Faculty of Science and Engineering > Biology
    Item ID: 21168
    Depositing User: IR eTheses
    Date Deposited: 05 Feb 2026 14:47
    Use Licence: This item is available under a Creative Commons Attribution Non Commercial Share Alike Licence (CC BY-NC-SA). Details of this licence are available here

    Downloads

    Downloads per month over past year

    Origin of downloads

    Repository Staff Only (login required)

    Item control page
    Item control page