Frequency and distribution of AP-1 sites in the human genome.
The AP-1-binding sequences are promoter/enhancer elements that play an essential role in the induction of many genes in mammalian cells; however, the number of genes containing AP-1 sites remains unknown. In order to better address the overall effect of AP-1 on expression of genes encoded by the entire genome, a genome-wide analysis of the frequency and distribution of AP-1 sites would be useful; yet to date, no such analysis of AP-1 sites or any other promoter/enhancer elements has been performed. We present here our study of the consensus AP-1 site and two single-bp variants showing that the frequency of AP-1 sites in promoter regions is significantly lower than their average rate of occurrence in the whole genomic sequence, as well as the frequency of a random heptanucleotide suggesting that nature has selected for a decrease in the frequency of AP-1 sites in the regulatory regions of genes. In addition, genes containing multiple AP-1 sites are more prevalent than those containing only one copy of an AP-1 site, which again may have evolved to allow for greater signal amplification or integration in the regulation of AP-1 target genes. However, the number of AP-1-regulated genes identified in various studies is far smaller than the number of genes containing potential AP-1 sites, indicating that not all AP-1 sites are activated in a given cell under a given condition, and is consistent with the prediction by others that cellular context determines which AP-1 sites are targeted by AP-1.
Zhou
Huamin
H
The Key Laboratory of the Ministry of Education for Cell Biology and Tumor Cell Engineering, School of Life Sciences, Xiamen University, Xiamen, Fujian, China.
Zarubin
Tyler
T
Ji
Zhiliang
Z
Min
Zheng
Z
Zhu
Wei
W
Downey
Jocelyn S
JS
Lin
Shengcai
S
Han
Jiahuai
J
D002877:Chromosomes, Human / Q000235:genetics*; D015894:Genome, Human; D006801:Humans; D011401:Promoter Regions, Genetic; D012045:Regulatory Sequences, Nucleic Acid; D018808:Transcription Factor AP-1 / Q000235:genetics*
D018808:Transcription Factor AP-1