GENERAL COMMENTARY article

Front. Genet., 20 March 2012

Sec. Evolutionary, Population, and Conservation Genetics

Volume 3 - 2012 | https://doi.org/10.3389/fgene.2012.00040

P53 Binding Sites in Transposons

  • TZ

    Tomasz Zemojtel *

  • MV

    Martin Vingron

  • Department of Computational Molecular Biology, Max-Planck-Institute for Molecular Genetics Berlin, Germany

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 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

CloneaGenomic location (hg19)NameFamilyClass
s57chr13: 114536915–114536965–––
N22chr11: 44182113–44182162–––
11A2chr14: 100093893–100093943–––
W211chr6: 116275323–116275368L2aL2LINE
W7B2chr13: 52641535–52641585MER61EERV1LTR
3Hchr2: 191494065–191494114HSMAR2TcMar-MarinerDNA
8Achr4: 15767109–15767147L2aL2LINE
532chr6: 170765704–170765758–––
64A2chr6: 88193436–88193496HERVIP10FHERV1LTR
W7A1chr7: 22821881–22821930–––
S61chr2: 32539190–32539238L1ME3BL1LINE
1183chr10: 121965614–121965661–––
N42chr7: 47737939–47737989–––
S201chr12: 113554293–113554341–––
S1503chr17: 9443256–9443316–––
S92Ichr19: 44049878–44049927–––
S592IIchr19: 44049787–44049836–––
2Nbchr6: 40151946–40151995LTR10B1ERV1LTR
9Hchr4: 49630288–49630337–––
CBE10dUn_gl000220: 101981–102031(CCTTG) nrepeat––

Characterization of 20 sequences reported by el-Deiry et al. (1992).

aClone names, as originally 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?

References

  • 1

    CuiF.SirotinM. V.ZhurkinV. B. (2011). Impact of Alu repeats on the evolution of human p53 binding sites. Biol. Direct6, 2.10.1186/1745-6150-6-2

  • 2

    el-DeiryW. S.KernS. E.PietenpolJ. A.KinzlerK. W.VogelsteinB. (1992). Definition of a consensus binding site for p53. Nat. Genet.1, 45–49.10.1038/ng0492-45

  • 3

    FeschotteC. (2008). Transposable elements and the evolution of regulatory networks. Nat. Rev. Genet.9, 397–405.10.1038/nrg2337

  • 4

    HarrisC. R.DewanA.ZupnickA.NormartR.GabrielA.PrivesC.LevineA. J.HohJ. (2009). p53 responsive elements in human retrotransposons. Oncogene28, 3857–3865.10.1038/onc.2009.246

  • 5

    JeggaA. G.IngaA.MenendezD.AronowB. J.ResnickM. A. (2008). Functional evolution of the p53 regulatory network through its target response elements. Proc. Natl. Acad. Sci. U.S.A.105, 944–949.10.1073/pnas.0704694105

  • 6

    SchmidtD.SchwalieP. C.WilsonM. D.BallesterB.GonçalvesA.KutterC.BrownG. D.MarshallA.FlicekP.OdomD. T. (2012). Waves of retrotransposon expansion remodel genome organization and CTCF binding in multiple mammalian lineages. Cell148, 335–348.10.1016/j.cell.2011.11.058

  • 7

    WangT.ZengJ.LoweC. B.SellersR. G.SalamaS. R.YangM.BurgessS. M.BrachmannR. K.HausslerD. (2007). Species-specific endogenous retroviruses shape the transcriptional network of the human tumor suppressor protein p53. Proc. Natl. Acad. Sci. U.S.A.104, 18613–18618.10.1073/pnas.0703676104

  • 8

    ZemojtelT.KielbasaS. M.ArndtP. F.ChungH. R.VingronM. (2009). Methylation and deamination of CpGs generate p53-binding sites on a genomic scale. Trends Genet.25, 63–66.10.1016/j.tig.2008.11.005

Summary

Keywords

evolution of gene regulatory motifs, genomic impact of transposons, p53, transcription factor binding sites

Citation

Zemojtel T and Vingron M (2012) P53 Binding Sites in Transposons. Front. Gene. 3:40. doi: 10.3389/fgene.2012.00040

Received

22 February 2012

Accepted

01 March 2012

Published

20 March 2012

Volume

3 - 2012

Copyright

*Correspondence:

This article was submitted to Frontiers in Evolutionary and Population Genetics, a specialty of Frontiers in Genetics.

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All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.

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