Xi Hualin, Shulha Hennady P, Lin Jane M, Vales Teresa R, Fu Yutao, Bodine David M, McKay Ronald D G, Chenoweth Josh G, Tesar Paul J, Furey Terrence S, Ren Bing, Weng Zhiping, Crawford Gregory E
Bioinformatics Program, Boston University, Boston, Massachusetts, United States of America.
PLoS Genet. 2007 Aug;3(8):e136. doi: 10.1371/journal.pgen.0030136. Epub 2007 Jul 2.
The identification of regulatory elements from different cell types is necessary for understanding the mechanisms controlling cell type-specific and housekeeping gene expression. Mapping DNaseI hypersensitive (HS) sites is an accurate method for identifying the location of functional regulatory elements. We used a high throughput method called DNase-chip to identify 3,904 DNaseI HS sites from six cell types across 1% of the human genome. A significant number (22%) of DNaseI HS sites from each cell type are ubiquitously present among all cell types studied. Surprisingly, nearly all of these ubiquitous DNaseI HS sites correspond to either promoters or insulator elements: 86% of them are located near annotated transcription start sites and 10% are bound by CTCF, a protein with known enhancer-blocking insulator activity. We also identified a large number of DNaseI HS sites that are cell type specific (only present in one cell type); these regions are enriched for enhancer elements and correlate with cell type-specific gene expression as well as cell type-specific histone modifications. Finally, we found that approximately 8% of the genome overlaps a DNaseI HS site in at least one the six cell lines studied, indicating that a significant percentage of the genome is potentially functional.
识别不同细胞类型中的调控元件对于理解控制细胞类型特异性基因和管家基因表达的机制至关重要。绘制DNaseI超敏（HS）位点图谱是识别功能性调控元件位置的一种准确方法。我们使用一种名为DNase芯片的高通量方法，从六种细胞类型中跨越人类基因组的1%识别出3904个DNaseI HS位点。在所有研究的细胞类型中，每种细胞类型中相当数量（22%）的DNaseI HS位点普遍存在。令人惊讶的是，几乎所有这些普遍存在的DNaseI HS位点都对应于启动子或绝缘子元件：其中86%位于注释的转录起始位点附近，10%与CTCF结合，CTCF是一种具有已知增强子阻断绝缘子活性的蛋白质。我们还识别出大量细胞类型特异性的DNaseI HS位点（仅存在于一种细胞类型中）；这些区域富含增强子元件，并且与细胞类型特异性基因表达以及细胞类型特异性组蛋白修饰相关。最后，我们发现，在所研究的六种细胞系中，至少有一种细胞系中约8%的基因组与DNaseI HS位点重叠，这表明基因组中有相当比例可能具有功能。
