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P53 Binding Sites in Transposons

Authors: Zemojtel, T.; Vingron, M.;

P53 Binding Sites in Transposons

Abstract

Repeated regions of the genome harbor more functional information than commonly assumed. Two decades ago, a highly influential paper describing the consensus binding site for the key transcription factor p53 was published in Nature Genetics by el-Deiry et al. (1992). Recently, it has been observed that many p53 binding sites are species-specific (Jegga et al., 2008), suggesting a remarkable flexibility in the p53 gene regulatory network. Consistent with this idea, several recent studies have reported the existence of p53 binding sites in sequences of primate-specific interspersed repeats, including retroviral long terminal repeats (LTRs; Wang et al., 2007), short (Alus;Zemojtel et al., 2009; Cui et al., 2011), and long interspersed nuclear elements (LINEs; Harris et al., 2009), highlighting the role of transposition in the emergence of cis-regulatory elements (Feschotte, 2008; Schmidt et al., 2012). We reanalyzed the 20 genomic sequences originally used by el-Deiry et al. (1992) to construct the p53 consensus binding motif. All of these binding sites could be uniquely mapped to the reference human genome sequence (hg19). Strikingly, as many as seven of these binding sites (∼35%) reside in one of three repeat classes: LTR, LINE, and DNA transposons (Table ​(Table1).1). Interestingly, this small set includes members of the primate-specific LTR10 and MER61 families, which were previously identified as enriched in copies with a functional p53 site (Wang et al., 2007). Additionally, we found that one of the early reported p53 binding sites is composed of a low-complexity repeat. Table 1 Characterization of 20 sequences reported by el-Deiry et al. (1992). In summary, the original work of el-Deiry et al. (1992) published 20 years ago already contained evidence for the involvement of transposable elements in spreading species-specific p53 binding sites. This raised the question: how many more gems are hidden in previously generated data sets?

Keywords

p53, evolution of gene regulatory motifs, transcription factor binding sites, genomic impact of transposons, Genetics, QH426-470

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citations
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
5
Average
Average
Average
Green
gold