The role of Nucleoporin TPR in cell functioning and differentiation

• Název práce v češtině: Role nukleoporinu TPR v buněčném fungování a diferenciaci
• Název v anglickém jazyce: The role of Nucleoporin TPR in cell functioning and differentiation
• Klíčová slova: Nukleoporiny, genová exprese, transkokated promotor region, TPR, LSD1, svalová diferenciace, Myh4, Olfr
• Klíčová slova anglicky: Nucleoporins; gene expression; translocated promoter region; TPR; LSD1; myogenic differentiation; Myh4; Olfr
• Akademický rok vypsání: 2016/2017
• Typ práce: disertační práce
• Jazyk práce: angličtina
• Ústav: Akademie věd ČR (11-00048)
• Vedoucí / školitel: Mgr. Jindřiška Fišerová, Ph.D.
• Řešitel: skrytý - zadáno a potvrzeno stud. odd.
• Datum přihlášení: 12.10.2016
• Datum zadání: 12.10.2016
• Datum potvrzení stud. oddělením: 12.10.2016
• Datum a čas obhajoby: 17.01.2024 13:00
• Místo konání obhajoby: Viničná 7, Praha 2, budova PřF
• Datum odevzdání elektronické podoby: 11.09.2023
• Datum proběhlé obhajoby: 17.01.2024
• Předmět: Obhajoba dizertační práce (B90002)
• Oponenti: MUDr. Libor Macůrek, Ph.D.

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Předběžná náplň práce

TPR je velký nukleoporin, který tvoří košík jaderného póru, a který byl předchozím výzkumem spjat s tvorbou nukleoskeletu. Interaguje s exportovanými molekulami, jadernou laminou i s vnitřkem jádra a má tak strategickou pozici propojovat všemožné buněčně procesy. Naše data poskytují podrobné informace o distribuci TPR uvnitř jádra a o povaze TPR nukleoskeletálních vláken. Dále pak rozšiřují i naše ponětí o funkci TPR v kontextu jaderných pórů jako centrálních uzlů pro transkripční regulaci.
Skrze ChIP-seq analýzu odhalujeme vazbu TPR k doménám chromatinu asociovanými s laminem (LADs). Zároveň ale ukazujeme, že na rozdíl od Laminu, má TPR na expresi asociovaných myogenních genů pozitivní vliv. Ukazujeme, že TPR tvoří komplex s LSD1 a přispívá k regulaci exprese alespoň některých z asociovaných genů skrze tuto interakci. Deplece TPR pak ovlivňuje svalovou diferenciaci, což opět zdůrazňuje klíčovou roli TPR v buněčných procesech.

Předběžná náplň práce v anglickém jazyce

TPR is a large nucleoporin located in the nuclear basket of the nuclear pore that was proposed to form nucleoskeleton. It interacts with exported molecules, components of the nuclear lamina, and the nuclear interior, positioning itself strategically to facilitate connections between various cellular processes. Our findings offer detailed insights into the distribution of TPR within the nucleus and the nature of TPR nucleoskeletal fibers. Furthermore, we enhance our understanding of TPR's function in the context of nuclear pore complexes (NPCs) as central hubs for transcriptional regulation.
Through ChIP-seq analysis, we uncover TPR's association with lamina-associated domains within chromatin. Intriguingly, we demonstrate that unlike lamin, TPR exerts a positive influence on genes involved in myogenesis. We further report that LSD1 forms a complex with TPR and takes a part in the regulation of the TPR associated genes. Finally, our data demonstrate that depletion of TPR adversely affects myogenic differentiation, underscoring its crucial involvement in essential cellular processes.