Yang Annie, Zhu Zhou, Kapranov Philipp, McKeon Frank, Church George M, Gingeras Thomas R, Struhl Kevin
Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts 02115, USA.
Mol Cell. 2006 Nov 17;24(4):593-602. doi: 10.1016/j.molcel.2006.10.018.
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.
通过使用覆盖整个人类基因组的平铺式微阵列，我们确定了约5800个p63的靶位点，p63是分层上皮发育所必需的p53同源物。p63的靶标富含参与细胞黏附、增殖、死亡和信号通路的基因。p63靶标的衍生DNA序列基序质量与体内结合强度相关，但基因组中只有一小部分基序被p63结合。相反，许多p63靶标的基序得分与随机基因组区域预期的得分相同。因此，p63在体内的结合具有高度选择性，通常需要简单蛋白质-DNA相互作用之外的其他因素。p63靶位点与p63反应性基因之间存在显著但复杂的关系，DeltaNp63亚型与转录激活相关。许多p63结合区域在进化上是保守的和/或与其他转录因子的序列基序相关，这表明很大一部分p63位点具有生物学相关性。
