| Summary: | 碩士 === 國立陽明大學 === 生命科學系暨基因體科學研究所 === 101 === TAR-DNA-binding protein-43 (TDP-43) is a ubiquitously expressed nuclear protein with multiple cellular functions. TDP-43 has been identified as the disease hallmark of frontotemporal dementia (FTLD-U) and amyotrophic lateral sclerosis (ALS). In these patients, TDP-43 is absent in the nucleus but forms aggregates in the cytoplasm. Therefore, loss of normal cellular functions of TDP-43 may play a role in these neurodegenerative diseases. Under normal condition, TDP-43 is often linked with regulation of pre-mRNA splicing, primary miRNA processing and mRNA stability. Although a few studies suggest that TDP-43 functions on transcriptional repression through binding to the promoter regions of human HIV-1 and mouse acrv1 genes, whether TDP-43 affects chromatin activity remains obscure. In this study, we aim to identify the possibility of chromatin regulation that TDP-43 may involve in. According to our finding, dTDP may involve in regulation of heterochromatin establishment and affect methylation level of H3K9. Also, we found gain of toxic function of dTDP would damage the higher-order chromosome structure.
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