Relationships between p63 binding, DNA sequence, transcription activity, and biological function in human cells

Yang, A., Zhu, Z., Kapranov, P., McKeon, F., Church, G. M., Gingeras, T. R., Struhl, K. (2006) Relationships between p63 binding, DNA sequence, transcription activity, and biological function in human cells. Molecular Cell, 24 (4). pp. 593-602. ISSN 10972765 (ISSN)

DOI: 10.1016/j.molcel.2006.10.018


Using tiled microarrays covering the entire human genome, we identify ∼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 ΔNp63 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. ©2006 Elsevier Inc.

Item Type: Paper
Uncontrolled Keywords: DNA isoprotein protein p53 protein p63 transcription factor DNA binding protein TP73L protein, human transactivator protein tumor suppressor protein amino acid sequence article cell adhesion cell death cell proliferation correlation analysis development DNA sequence epithelium female gene genetic conservation genome human human cell in vivo study molecular biology mouse nonhuman protein binding protein DNA interaction protein motif protein targeting rat strength transcription initiation apoptosis binding site cell line genetic transcription genetics metabolism nucleotide sequence signal transduction Binding Sites Conserved Sequence DNA-Binding Proteins Genome Human Humans Trans-Activators Transcription Genetic Tumor Suppressor Protein p53 Tumor Suppressor Proteins
Subjects: bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > DNA expression
bioinformatics > genomics and proteomics > analysis and processing > microarray gene expression processing
bioinformatics > genomics and proteomics > annotation > sequence annotation
CSHL Authors:
Communities: CSHL labs > Gingeras lab
Depositing User: CSHL Librarian
Date: 2006
Date Deposited: 08 Mar 2012 17:19
Last Modified: 15 Jul 2013 14:29
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