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.
Preview
Available under License Creative Commons Attribution Non-commercial Share Alike.
Download (102MB) | Preview
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
Share and Export
Share and Export