|
|
Evolutionarily conserved mechanisms of gene expression regulation by nuclear receptors.
Chughtai, Ahmed Ali ; Kostrouch, Zdeněk (advisor) ; Malínský, Jan (referee) ; Brábek, Jan (referee)
Transcriptional regulation of gene expression in eukaryotes has evolved over millions of years. The regulatory pathways of nuclear receptors represent an evolutionarily ancient, but conserved mechanism with associated accessory proteins, many of them forming a functional nexus known as the Mediator complex involved in transcription. Despite the versatility of the pathway, e.g. through the adoption of new regulatory functions in phylogenetically more recent Metazoa, we hypothesise that the intrinsic potential of the NR-Mediator axis to directly translate a stimulus to a biological response is conserved across species, and additional regulation could also be achieved through secondary functions of its essential members. To support the hypothesis, we assessed the ligand-binding capability of retinoic X receptor in Trichoplax adhaerens and provided evidence to support the concept that this capability was already present at the base of metazoan evolution. With regards to the potential secondary functions, we took inspiration from previous research and identified the Mediator subunit 28 (MED28) as the only known member having documented nuclear and cytoplasmic dual roles, and thus possessing the potential to transmit signals from the cellular structural states to the nucleus. Due to the lack of...
|
|
|
Conserved Mechanisms of Gene Expression Regulation by Nuclear Receptors.
Novotný, Jan Philipp ; Kostrouch, Zdeněk (advisor) ; Stopka, Pavel (referee) ; Lazar, Jozef (referee)
7 Abstract With the first appearance of life on Earth, organisms had to adapt to an ever-changing surrounding environment in order to survive. Since the emergence of metazoan multi- cellularity, subsets of cells could adapt to perform specific biological tasks beneficial to the whole organism, necessitating not only spatiotemporal regulation of gene expression during development, but also integration of tissue specific needs with overall organis- mal status. Within the set of evolutionary conserved regulatory systems, the family of nuclear receptor (NR) transcription factors stands out due to its high degree of evolu- tionary conservation, plasticity and uniqueness to the metazoan kingdom, regulating gene expression in response to, or in the absence of a ligand by genomic and non- genomic actions. With an increasing number of different compounds being recognized as ligands to NRs, it is now thought that ancient NRs were probably characterized by low ligand binding specificity, eventually serving as environmental sensors, integrating nutrient availability and gene expression at the base of metazoan evolution. Characteri- zation of the NR network in one of the simplest metazoan organisms, Trichoplax ad- haerens, revealed not only a functional network and sub-specialization of NR dependent gene regulation, but...
|
guest ::
