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Analysis of genomic regions bound and regulated by Ataxin-3
Svoreň, Martin ; Čečková, Martina (advisor) ; Hofman, Jakub (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology and Toxicology Student: Martin Svoreň Supervisor: PharmDr. Martina Čečková, Ph.D. Specialized supervisor: PD Dr. Bernd Evert Title of diploma thesis: Analysis of genomic regions bound and regulated by Ataxin-3 Spinocerebellar ataxia type 3 (SCA3), also known as Machado-Joseph disease, is a dominantly inherited neurodegenerative disease. In SCA3, the disease protein ataxin-3 (ATXN3) contains an abnormally long polyglutamine (polyQ) tract encoded by CAG repeat expansion. ATXN3 binds DNA and interacts with transcriptional regulators pointing toward a direct role of ATXN3 in transcription. It is conceivable that mutant ATXN3 triggers multiple, interconnected pathogenic cascades leading to neurotoxicity, however, the principal molecular pathomechanism remains elusive. Here, PCR analyses of 16 ATXN3-bound genomic regions recently identified by next generation sequencing of immunoprecipitated ATXN3-bound chromatin fragments confirmed enriched binding of ATXN3 to 5 genomic regions next to genes encoding CCAAT/enhancer binding protein delta (CEBPD), period circadian clock-2 (PER2), phosphatase and tensin homolog (PTEN), serine protease inhibitor family F2 (SERPINF2) and thrombospondin-1 (THBS1). To investigate putative...
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