Tuyển tập báo cáo các nghiên cứu khoa học quốc tế ngành y học dành cho các bạn tham khảo đề tài: High-throughput sequencing identifies STAT3 as the DNA-associated factor for p53-NF-κB-complex-dependent gene expression in human heart failure | Choy et al. Genome Medicine 2010 2 37 http content 2 6 37 RESEARCH Open Access High-throughput sequencing identifies STAT3 as the DNA-associated factor for p53-NF-KB-complex-dependent gene expression in human heart failure Mun-Kit Choy 1 Mehregan Movassagh1 Lee Siggens1 Ana Vujic1 Martin Goddard2 Ana Sanchez3 Neil Perkins3 Nichola Figg1 Martin Bennett1 Jason Carroll4 and Roger Foo 1 Abstract Background Genome-wide maps of DNA regulatory elements and their interaction with transcription factors may form a framework for understanding regulatory circuits and gene expression control in human disease but how these networks comprising transcription factors and DNA-binding proteins form complexes interact with DNA and modulate gene expression remains largely unknown. Methods Using microRNA-21 mir-21 which is an example of genes that are regulated in heart failure we performed chromatin immunoprecipitation ChIP assays to determine the occupancy of transcription factors at this genetic locus. Tissue ChIP was further performed using human hearts and genome-wide occupancies of these transcription factors were analyzed by high-throughput sequencing. Results We show that the transcription factor p53 piggy-backs onto NF-kB RELA and utilizes the KB-motif at a cis-regulatory region to control mir-21 expression. p53 behaves as a co-factor in this complex because despite a mutation in its DNA binding domain mutant p53 was still capable of binding RELA and the cis-element and inducing mir-21 expression. In dilated human hearts where mir-21 upregulation was previously demonstrated the p53-RELA complex was also associated with this cis-element. Using high-throughput sequencing we analyzed genome-wide binding sites for the p53-RELA complex in diseased and control human hearts and found a significant overrepresentation of the STAT3 motif. We further determined that STAT3 was necessary for the p53-RELA complex to associate with this ciselement and for mir-21 expression.
