Relationships between p63 binding, DNA sequence, transcription activity, and biological function in human cells.
Using tiled microarrays covering the entire human genome, we identify approximately 5800 target sites for p63, a p53 homolog essential for stratified epithelial development. p63 targets are enriched for genes involved in cell adhesion, proliferation, death, and signaling pathways. The quality of the derived DNA sequence motif for p63 targets correlates with binding strength binding in vivo, but only a small minority of motifs in the genome is bound by p63. Conversely, many p63 targets have motif scores expected for random genomic regions. Thus, p63 binding in vivo is highly selective and often requires additional factors beyond the simple protein-DNA interaction. There is a significant, but complex, relationship between p63 target sites and p63-responsive genes, with DeltaNp63 isoforms being linked to transcriptional activation. Many p63 binding regions are evolutionarily conserved and/or associated with sequence motifs for other transcription factors, suggesting that a substantial portion of p63 sites is biologically relevant.
Yang
Annie
A
Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts 02115, USA.
Zhu
Zhou
Z
Kapranov
Philipp
P
McKeon
Frank
F
Church
George M
GM
Gingeras
Thomas R
TR
Struhl
Kevin
K
D017209:Apoptosis / Q000235:genetics; D001665:Binding Sites / Q000235:genetics; D002448:Cell Adhesion / Q000235:genetics; D002460:Cell Line; D049109:Cell Proliferation; D017124:Conserved Sequence / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D015894:Genome, Human; D006801:Humans; D011485:Protein Binding; D015398:Signal Transduction / Q000235:genetics; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors; D014158:Transcription, Genetic; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*
D004268:DNA-Binding Proteins; C115051:TP63 protein, human; D015534:Trans-Activators; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins