Sbisà Elisabetta, Catalano Domenico, Grillo Giorgio, Licciulli Flavio, Turi Antonio, Liuni Sabino, Pesole Graziano, De Grassi Anna, Caratozzolo Mariano Francesco, D'Erchia Anna Maria, Navarro Beatriz, Tullo Apollonia, Saccone Cecilia, Gisel Andreas
Istituto di Tecnologie Biomediche-Sede di Bari, CNR, Via Amendola, 122/D 70126 Bari, Italy.
BMC Bioinformatics. 2007 Mar 8;8 Suppl 1(Suppl 1):S20. doi: 10.1186/1471-2105-8-S1-S20.
The p53 gene family consists of the three genes p53, p63 and p73, which have polyhedral non-overlapping functions in pivotal cellular processes such as DNA synthesis and repair, growth arrest, apoptosis, genome stability, angiogenesis, development and differentiation. These genes encode sequence-specific nuclear transcription factors that recognise the same responsive element (RE) in their target genes. Their inactivation or aberrant expression may determine tumour progression or developmental disease. The discovery of several protein isoforms with antagonistic roles, which are produced by the expression of different promoters and alternative splicing, widened the complexity of the scenario of the transcriptional network of the p53 family members. Therefore, the identification of the genes transactivated by p53 family members is crucial to understand the specific role for each gene in cell cycle regulation. We have combined a genome-wide computational search of p53 family REs and microarray analysis to identify new direct target genes. The huge amount of biological data produced has generated a critical need for bioinformatic tools able to manage and integrate such data and facilitate their retrieval and analysis.
We have developed the p53FamTaG database (p53 FAMily TArget Genes), a modular relational database, which contains p53 family direct target genes selected in the human genome searching for the presence of the REs and the expression profile of these target genes obtained by microarray experiments. p53FamTaG database also contains annotations of publicly available databases and links to other experimental data. The genome-wide computational search of the REs was performed using PatSearch, a pattern-matching program implemented in the DNAfan tool. These data were integrated with the microarray results we produced from the overexpression of different isoforms of p53, p63 and p73 stably transfected in isogenic cell lines, allowing the comparative study of the transcriptional activity of all the proteins in the same cellular background.p53FamTaG database is available free at http://www2.ba.itb.cnr.it/p53FamTaG/ CONCLUSION: p53FamTaG represents a unique integrated resource of human direct p53 family target genes that is extensively annotated and provides the users with an efficient query/retrieval system which displays the results of our microarray experiments and allows the export of RE sequences. The database was developed for supporting and integrating high-throughput in silico and experimental analyses and represents an important reference source of knowledge for research groups involved in the field of oncogenesis, apoptosis and cell cycle regulation.
p53基因家族由p53、p63和p73这三个基因组成，它们在DNA合成与修复、生长停滞、细胞凋亡、基因组稳定性、血管生成、发育和分化等关键细胞过程中具有多方面且不重叠的功能。这些基因编码序列特异性核转录因子，它们能识别靶基因中相同的反应元件（RE）。它们的失活或异常表达可能决定肿瘤进展或发育性疾病。由不同启动子表达和可变剪接产生的几种具有拮抗作用的蛋白质异构体的发现，增加了p53家族成员转录网络情况的复杂性。因此，鉴定由p53家族成员反式激活的基因对于理解每个基因在细胞周期调控中的特定作用至关重要。我们结合了对p53家族REs的全基因组计算搜索和微阵列分析来鉴定新的直接靶基因。所产生的大量生物学数据迫切需要能够管理和整合此类数据并便于其检索和分析的生物信息学工具。
我们开发了p53FamTaG数据库（p53家族靶基因数据库），这是一个模块化关系数据库，其中包含在人类基因组中通过搜索REs的存在而选择的p53家族直接靶基因，以及通过微阵列实验获得的这些靶基因的表达谱。p53FamTaG数据库还包含公共可用数据库的注释以及到其他实验数据的链接。使用DNAfan工具中实现的模式匹配程序PatSearch对REs进行全基因组计算搜索。这些数据与我们从稳定转染到同基因细胞系中的p53、p63和p73不同异构体的过表达产生的微阵列结果相结合，从而能够在相同细胞背景下对所有蛋白质的转录活性进行比较研究。p53FamTaG数据库可在http://www2.ba.itb.cnr.it/p53FamTaG/免费获取。
p53FamTaG代表了人类p53家族直接靶基因的独特综合资源，该资源经过广泛注释，并为用户提供了一个高效的查询/检索系统，该系统显示我们微阵列实验的结果并允许导出RE序列。该数据库是为支持和整合高通量计算机模拟和实验分析而开发的，是参与肿瘤发生、细胞凋亡和细胞周期调控领域的研究小组的重要知识参考来源。
