Rola białka ATRX w organizacji chromatyny neuronów hipokampa mózgu szczura : praca doktorska

Holm-Kaczmarek, Dagmara

Skip to main menu
Skip to search engine
Skip to content
Skip to footer

Rola białka ATRX w organizacji chromatyny neuronów hipokampa mózgu szczura : praca doktorska

Download

Description
Information

Title: Rola białka ATRX w organizacji chromatyny neuronów hipokampa mózgu szczura : praca doktorska

Abstract:

The ATRX (alpha thalassemia mental retardation syndrome X-linked) protein is an important protein that maintains chromatin structure with helicase properties. Its presence appears to be particularly important in neural tissue, as mutations in the Atrx gene lead to alpha thalassemia mental retardation syndrome X-linked (ATRX) characterized by, among other things, mental retardation. Despite these observations, the function of the ATRX protein in neurons is still poorly understood. Literature data suggest that the main function of this protein is participation in chromatin remodeling and DNA sequence silencing. However, there are also reports indicating its role in the activation of gene expression, demonstrating its important but ambiguous role. My preliminary studies on the occurrence of ATRX protein in hippocampal neurons confirmed its localization in condensed DNA regions. Therefore, the purpose of this dissertation was to determine the localization and role of the ATRX protein in the cell nucleus of neurons in the resting state and after stimulation. I pursued this goal using primary culture of hippocampal neurons subjected to a procedure for chemically inducing long term potentiation (cLTP). Analysis of the ATRX protein localization in the nucleus of neurons showed that in the resting state ATRX localizes at chromatin, colocalizing with chromocenters, while after cLTP evoking it accompanies changes in chromatin organization by surrounding chromatin clusters or colocalizing with them as well as with euchromatin markers, indicating an ambiguous role for ATRX in neurons. In contrast, silencing of Atrx in neurons leads to changes in chromatin organization manifested by increased chromatin condensation, accompanied by changes in the pattern of post-translational modifications of histones. In addition, I identified a new nucleolar structure composed of the ATRX protein, which is required for its maintenance. I also showed that silencing of Atrx results in functional changes in neurons, as reflected by changes in the morphology of dendritic trees, which become smaller and less spread out. In conclusion, my results indicate that ATRX protein plays an important role in neurons in the organization of chromatin and nucleolar structures, and the possible relationship between chromatin structure and cell morphology requires further research.