Wang Min, Gu Chunsheng, Qi Tianyang, Tang Wen, Wang Ling, Wang Shuyan, Zeng Xianlu
Institute of Genetics and Cytology, Northeast Normal University, Changchun, China.
J Biochem. 2007 Nov;142(5):613-20. doi: 10.1093/jb/mvm176. Epub 2007 Sep 18.
BAF53, a component of chromatin remodelling and histone acetyltransferase complexes, has been shown to be essential for cell survival in human cells and plays roles in p53-mediated gene transcription. However, the mechanism concerned in the process needs to be further explored. In this study, we show that BAF53 is involved in the repression of p53-dependent p21-gene transcription by interacting with p53 both in vivo and in vitro. Through electrophoretic mobility shift assay (EMSA) and chromatin immunoprecipitation analyses, we demonstrate that BAF53 can reduce the p53-binding ability to p21 promoter. By western-blot experiments, we find that BAF53 can decrease p53-Lys382 acetylation, which may be partially responsible for the repression of p53-binding ability. Furthermore, BAF53 represses p21-promoter activity in a BRG1-independent manner. These data contribute to elucidating the molecular mechanisms of BAF53 in regulating p53-mediated gene transcription.
BAF53是染色质重塑和组蛋白乙酰转移酶复合物的一个组成部分,已被证明对人类细胞的存活至关重要,并在p53介导的基因转录中发挥作用。然而,该过程中涉及的机制仍需进一步探索。在本研究中,我们发现BAF53在体内和体外均通过与p53相互作用参与对p53依赖的p21基因转录的抑制。通过电泳迁移率变动分析(EMSA)和染色质免疫沉淀分析,我们证明BAF53可降低p53与p21启动子的结合能力。通过蛋白质免疫印迹实验,我们发现BAF53可降低p53-Lys382的乙酰化水平,这可能是其抑制p53结合能力的部分原因。此外,BAF53以不依赖BRG1的方式抑制p21启动子活性。这些数据有助于阐明BAF53在调节p53介导的基因转录中的分子机制。