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AbstractMammalian promoters can be separated into two classes, conserved TATA box–enriched promoters, which initiate at a well-defined site, and more plastic, broad and evolvable CpG-rich promoters. We have sequenced tags corresponding to several hundred thousand transcription start sites (TSSs) in the mouse and human genomes, allowing precise analysis of the sequence architecture and evolution of distinct promoter classes. Different tissues and families of genes differentially use distinct types of promoters. Our tagging methods allow quantitative analysis of promoter usage in different tissues and show that differentially regulated alternative TSSs are a common feature in protein-coding genes and commonly generate alternative N termini. Among the TSSs, we identified new start sites associated with the majority of exons and with 3' UTRs. These data permit genome-scale identification of tissue-specific promoters and analysis of the cis-acting elements associated with them. NOTE: In the version of this article initially published online, the x-axis of Figure 4b was mislabeled. Specifically, the five groups on the x-axis should be labeled: No mutation PyPu to PuPu PyPu to PuPy PyPu to PyPu PyPu to PyPy The error has been corrected for all versions of the article. NOTE: In the version of this article initially published, two of the smaller bar plots in Figure 1e were mistakenly duplicated. Specifically, the Zfp385 plot is an erroneous copy of the 137774 plot, and the Txndc7 plot is an erroneous copy of the Pik3r5 plot. See below for the corrected version of the figure. This error does not change the conclusions of the study in any way, as the bar plots are just a few visual examples of more than 5,000 tag clusters, and the correct plots follow the same distribution patterns as the erroneous ones. This error has been corrected in the HTML and PDF versions of the article.
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