Research Institute of Molecular Pathology, 1030 Vienna, Austria.
Genes Dev. 2012 May 1;26(9):908-13. doi: 10.1101/gad.188052.112. Epub 2012 Apr 12.
HOT (highly occupied target) regions bound by many transcription factors are considered to be one of the most intriguing findings of the recent modENCODE reports, yet their functions have remained unclear. We tested 108 Drosophila melanogaster HOT regions in transgenic embryos with site-specifically integrated transcriptional reporters. In contrast to prior expectations, we found 102 (94%) to be active enhancers during embryogenesis and to display diverse spatial and temporal patterns, reminiscent of expression patterns for important developmental genes. Remarkably, HOT regions strongly activate nearby genes and are required for endogenous gene expression, as we show using bacterial artificial chromosome (BAC) transgenesis. HOT enhancers have a distinct cis-regulatory signature with enriched sequence motifs for the global activators Vielfaltig, also known as Zelda, and Trithorax-like, also known as GAGA. This signature allows the prediction of HOT versus control regions from the DNA sequence alone.
高度占据靶位（HOT）区域被许多转录因子结合，被认为是最近 modENCODE 报告中最有趣的发现之一，但它们的功能仍不清楚。我们在具有特异性整合转录报告器的转基因胚胎中测试了 108 个黑腹果蝇 HOT 区域。与之前的预期相反，我们发现 102 个（94%）在胚胎发生过程中是活跃的增强子，并显示出多样化的时空模式，类似于重要发育基因的表达模式。值得注意的是，HOT 区域强烈激活附近的基因，并被内源基因表达所必需，正如我们使用细菌人工染色体（BAC）转基因所展示的那样。HOT 增强子具有独特的顺式调控特征，富含 Vielfaltig（也称为 Zelda）和 Trithorax-like（也称为 GAGA）等全局激活因子的富集序列基序。这个特征允许仅从 DNA 序列预测 HOT 与对照区域。
