Genome-Wide Mapping Indicates That p73 and p63 Co-Occupy Target Sites and Have Similar DNA-Binding Profiles In Vivo
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Authors: | Annie Yang Zhou Zhu Arminja Kettenbach Philipp Kapranov Frank McKeon Thomas R Gingeras Kevin Struhl |
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Institution: | 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.;Institute of Genetics and Molecular and Cellular Biology, France |
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Abstract: | BackgroundThe p53 homologs, p63 and p73, share ∼85% amino acid identity in their DNA-binding domains, but they have distinct biological functions.Principal FindingsUsing 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.ConclusionsThe 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 involve functions other than DNA binding. |
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