Baniulyte Gabriele, Hicks Sawyer M, Sammons Morgan A
Department of Biological Sciences and The RNA Institute, University at Albany, State University of New York, Albany, NY 12222.
bioRxiv. 2024 Sep 25:2024.09.24.614594. doi: 10.1101/2024.09.24.614594.
The tumor suppressor gene encodes the DNA binding transcription factor p53 and is one of the most commonly mutated genes in human cancer. Tumor suppressor activity requires binding of p53 to its DNA response elements and subsequent transcriptional activation of a diverse set of target genes. Despite decades of close study, the logic underlying p53 interactions with its numerous potential genomic binding sites and target genes is not yet fully understood. Here, we present a database of DNA and chromatin-based information focused on putative p53 binding sites in the human genome to allow users to generate and test new hypotheses related to p53 activity in the genome. Users can query genomic locations based on experimentally observed p53 binding, regulatory element activity, genetic variation, evolutionary conservation, chromatin modification state, and chromatin structure. We present multiple use cases demonstrating the utility of this database for generating novel biological hypotheses, such as chromatin-based determinants of p53 binding and potential cell type-specific p53 activity. All database information is also available as a precompiled sqlite database for use in local analysis or as a Shiny web application.
肿瘤抑制基因编码DNA结合转录因子p53,是人类癌症中最常发生突变的基因之一。肿瘤抑制活性需要p53与其DNA反应元件结合,并随后对多种靶基因进行转录激活。尽管经过数十年的深入研究,但p53与其众多潜在基因组结合位点和靶基因相互作用的逻辑尚未完全理解。在这里,我们展示了一个基于DNA和染色质信息的数据库,重点关注人类基因组中假定的p53结合位点,以允许用户生成和测试与基因组中p53活性相关的新假设。用户可以根据实验观察到的p53结合、调控元件活性、遗传变异、进化保守性、染色质修饰状态和染色质结构来查询基因组位置。我们展示了多个用例,证明了该数据库在生成新的生物学假设方面的实用性,例如基于染色质的p53结合决定因素和潜在的细胞类型特异性p53活性。所有数据库信息也可作为预编译的sqlite数据库用于本地分析,或作为一个Shiny网络应用程序使用。