| The remodeling of the chromatin structure mediated by histone posttranslational modifications plays a crucial role in the expression regulation of eukaryotic genes. Among the histone posttranslational modifications, the histone acetylation catalyzed by histone acetyltransferases (HATs) and histone deacetylases (HDACs) plays a critical role in gene regulation and hence has been intensively studied. The reversible acetylation/deacetylation modification of lysine residues in core histone tails mediated by these two enzymes modulates the initiation of transcription, thus leads to the activation/suppression of gene expression. Transcriptional coactivators p300/CBP, which possess histone acetyltransferase activities, are involved in transcriptional regulation of many genes by distinct mechanisms.Nijmegen breakage syndrome (NBS) is an autosomal recessive hereditary disorder characterized by microcephaly, a"bird-like"facial appearance, growth retardation, immunodeficiency, radiosensitivity, chromosomal instability, and predisposition to tumor formation.The aim of this study was to clarify whether the histone acetylation modification participates in the regulation of NBS1 gene transcription and to explore its molecular mechanisms. By applying a series of transient transfection and relative luciferase activity assays, we found that histone acetyltransferases p300 promoted the activities of the NBS1 promoter. The results of RT-PCR and Western Blot confirmed the effects of p300 in promoting the NBS1 gene expression. Additionally, one functional c-myc site located in NBS1 promoter was identified.Data presented in this thesis demonstrated that the histone acetylation modification was involved in the transcriptional regulation of NBS1 gene. The molecular mechanisms of histone acetylation in NBS1 gene regulation were briefly exploited. This study provides further insight into the mechanisms of transcriptional regulation of NBS1 gene and the basis for studies of NBS1-associated diseases.
|
PDF Full Text Request