Clustering of DNA sequences in human promoters
Clustering of DNA sequences in human promoters
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DOI：
10.1101/gr.1953904
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发表时间：
2004-08-01
期刊：
影响因子：
7
通讯作者：
Vinson, C
中科院分区：
文献类型：
--
作者：
FitzGerald, PC;Shlyakhtenko, A;Vinson, C
我们已经确定了65，536个DNA序列中的每一个的分布，这些DNA序列在一组13，010个相对于假定的转录起始位点（TSS）排列的人类基因组启动子序列中是8个碱基长（8聚体）。有限数量的8聚体在其分布中具有峰（簇），并且大多数簇在TSS的100 bp内。在TSS附近表现出最大统计学显著聚类的156个DNA序列可以被置于9组相关序列中。每组由共有序列限定，并且这些共有序列中的七个是转录因子（TF）SPI、NF-Y、ETS、CREB、TBP、USF和NRF-1的已知结合位点。一个序列，我们称之为p53 1，不是已知的TF结合位点。第九序列组由聚集在TSS下游的链特异性Kozak序列组成。这些TF共有序列的共同出现的检查表明，除了由TBP（TATA框）结合的序列外，它们中的大多数呈正相关。来自29个组织的人mRNA表达数据表明，成簇的ETS、NRF-1和NRF 1序列主要存在于管家基因（例如，核糖体基因）。相比之下，TATA在组织特异性基因的启动子中更丰富。该分析在5082个启动子中确定了8个DNA序列，我们认为这些序列对调节基因表达很重要。
We have determined the distribution of each of the 65,536 DNA sequences that are eight bases long (8-mer) in a set of 13,010 human genomic promoter sequences aligned relative to the putative transcription start site (TSS). A limited number of 8-mers have peaks in their distribution (cluster), and most cluster within 100 by of the TSS. The 156 DNA sequences exhibiting the greatest statistically significant clustering near the TSS can be placed into nine groups of related sequences. Each group is defined by a consensus sequence, and seven of these consensus sequences are known binding sites for the transcription factors (TFs) SPI, NF-Y, ETS, CREB, TBP, USF, and NRF-1. One sequence, which we named Clusl, is not a known TF binding site. The ninth sequence group is composed of the strand-specific Kozak sequence that clusters downstream of the TSS. An examination of the co-occurrence of these TF consensus sequences indicates a positive correlation for most of them except for sequences bound by TBP (the TATA box). Human mRNA expression data from 29 tissues indicate that the ETS, NRF-1, and Clusl sequences that cluster are predominantly found in the promoters of housekeeping genes (e.g., ribosomal genes). In contrast, TATA is more abundant in the promoters of tissue-specific genes. This analysis identified eight DNA sequences in 5082 promoters that we suggest are important for regulating gene expression.