Relationships between p63 binding, DNA sequence, transcription activity, and biological function in human cells
Relationships between p63 binding, DNA sequence, transcription activity, and biological function in human cells
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DOI：
10.1016/j.molcel.2006.10.018
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发表时间：
2006-11-17
期刊：
影响因子：
16
通讯作者：
Struhl, Kevin
中科院分区：
文献类型：
--
作者：
Yang, Annie;Zhu, Zhou;Struhl, Kevin
使用覆盖整个人类基因组的平铺微阵列，我们确定了类似于5800个p63的靶位点，p53同源物对复层上皮发育至关重要。p63靶富集了参与细胞粘附、增殖、死亡和信号传导途径的基因。p63靶的衍生DNA序列基序的质量与体内结合强度相关，但基因组中只有少数基序与p63结合。相反，许多p63靶标具有随机基因组区域预期的基序得分。因此，p63在体内的结合是高度选择性的，并且通常需要除了简单的蛋白质-DNA相互作用之外的其他因素。在p63靶位点和p63应答基因之间存在显著但复杂的关系，其中Delta Np 63同种型与转录激活相关。许多p63结合区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p63位点的相当大一部分是生物学相关的。
Using tiled microarrays covering the entire human genome, we identify similar to 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 Delta Np63 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.