genome-wide mapping indicates that p73 and p63 co-occupy target sites and have similar dna-binding profiles in vivo全基因组映射表明p73和p63 co-occupy目标站点和有相似的dna结合蛋白体内.pdfVIP

Genome-Wide Mapping Indicates That p73 and p63 Co-Occupy Target Sites and Have Similar DNA-Binding Profiles In Vivo 1 2 3 4 3 Annie Yang , Zhou Zhu , Arminja Kettenbach , Philipp Kapranov , Frank McKeon , 4 1 Thomas R. Gingeras , Kevin Struhl * 1 Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts, United States of America, 2 Department of Genetics, Harvard Medical School, Boston, Massachusetts, United States of America, 3 Department of Cell Biology, Harvard Medical School, Boston, Massachusetts, United States of America, 4 Affymetrix, Santa Clara, California, United States of America Abstract Background: The p53 homologs, p63 and p73, share ,85% amino acid identity in their DNA-binding domains, but they have distinct biological functions. Principal Findings: Using chromatin immunoprecipitation and high-resolution tiling arrays covering the human genome, we identify p73 DNA binding sites on a genome-wide level in ME180 human cervical carcinoma cells. Strikingly, the p73 binding profile is indistinguishable from the previously described binding profile for p63 in the same cells. Moreover, the p73:p63 binding ratio is similar at all genomic loci tested, suggesting that there are few, if any, targets that are specific for one of these factors. As assayed by sequential chromatin immunoprecipitation, p63 and p73 co-occupy DNA target sites in vivo, suggesting that p63 and p73 bind primarily as heterotetrameric complexes in ME180 cells. Conclusions: The observation that p63 and p73 associate with the same genomic targets suggest that their distinct biological functions are due to cell-type specific expression and/or protein domains that inv