Vingron, Martin

Zemojtel, Tomasz

English

PubMed

Zemojtel, T.

Vingron, M.

MPG.PuRe

A commentary onDefinition of a consensus binding site for p53by el-Deiry, W. S., Kern, S. E., Pietenpol, J. A., Kinzler, K. W., and Vogelstein, B. (1992). Nat. Genet. 1, 45–49.Repeated regions of the genome harbor more functional information than commonly assumed. Two decades ago, a highly influ-ential paper describing the consensus bind-ing 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-spe-cific (Jegga et al., 2008), suggesting a remark-able 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 retro-viral 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), high-lighting the role of transposition in the emer-gence 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 fami-lies, 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-com-plexity repeat.In summary, the original work of el-Deiry et al. (1992) published 20 years ago already contained evidence for the involve-ment of transposable elements in spread-ing species-specific p53 binding sites. This raised the question: how many more gems are hidden in previously generated data sets?RefeRencesCui, F., Sirotin, M. V., and Zhurkin, V. B. (2011). Impact of Alu repeats on the evolution of human p53 binding sites. Biol. Direct 6, 2.el-Deiry, W. S., Kern, S. E., Pietenpol, J. A., Kinzler, K. W., and Vogelstein, B. (1992). Definition of a consensus binding site for p53. Nat. Genet. 1, 45–49.Feschotte, C. (2008). Transposable elements and the evolution of regulatory networks. Nat. Rev. Genet. 9, 397–405.Harris, C. R., Dewan, A., Zupnick, A., Normart, R., Gabriel, A., Prives, C., Levine, A. J., and Hoh, J. (2009). p53 responsive elements in human retrotransposons. Oncogene 28, 3857–3865.Jegga, A. G., Inga, A., Menendez, D., Aronow, B. J., and Resnick, M. A. (2008). Functional evolution of the p53 regulatory network through its target response elements. Proc. Natl. Acad. Sci. U.S.A. 105, 944–949.Schmidt, D., Schwalie, P. C., Wilson, M. D., Ballester, B., Gonçalves, A., Kutter, C., Brown, G. D., Marshall, A., Flicek, P., and Odom, D. T. (2012). Waves of retro-transposon expansion remodel genome organization and CTCF binding in multiple mammalian lineages. Cell 148, 335–348.Wang, T., Zeng, J., Lowe, C. B., Sellers, R. G., Salama, S. R., Yang, M., Burgess, S. M., Brachmann, R. K., and Haussler, D. (2007). Species-specific endogenous ret-roviruses shape the transcriptional network of the human tumor suppressor protein p53. Proc. Natl. Acad. Sci. U.S.A. 104, 18613–18618.Zemojtel, T., Kielbasa, S. M., Arndt, P. F., Chung, H. R., and Vingron, M. (2009). Methylation and deamination of CpGs generate p53-binding sites on a genomic scale. Trends Genet. 25, 63–66.Received: 22 February 2012; accepted: 01 March 2012; published online: 20 March 2012.Citation: Zemojtel T and Vingron M (2011) p53 bind-ing sites in transposons. Front. Gene. 3:40. doi: 10.3389/fgene.2012.00040This article was submitted to Frontiers in Evolutionary and Population Genetics, a specialty of Frontiers in Genetics.Copyright © 2011 Zemojtel and Vingron. This is an open-access article distributed under the terms of the Creative Commons Attribution Non Commercial License, which permits non-commercial use, distribution, and reproduc-tion in other forums, provided the original authors and source are credited.p53 binding sites in transposonsTomasz Zemojtel* and Martin VingronDepartment of Computational Molecular Biology, Max-Planck-Institute for Molecular Genetics, Berlin, Germany*Correspondence: zemojtel@molgen.mpg.deTable 1 | Characterization of 20 sequences reported by el-Deiry et al. (1992).Clonea Genomic location (hg19) Name Family Classs57 chr13: 114536915–114536965 – – –N22 chr11: 44182113–44182162 – – –11A2 chr14: 100093893–100093943 – – –W211 chr6: 116275323–116275368  L2a L2 LINEW7B2 chr13: 52641535–52641585 MER61E ERV1 LTR3H chr2: 191494065–191494114 HSMAR2 TcMar-Mariner DNA8A chr4: 15767109–15767147 L2a L2 LINE532 chr6: 170765704–170765758 – – –64A2 chr6: 88193436–88193496 HERVIP10FH ERV1 LTRW7A1 chr7: 22821881–22821930 – – –S61 chr2: 32539190–32539238 L1ME3B L1 LINE1183 chr10: 121965614–121965661 – – –N42 chr7: 47737939–47737989 – – –S201 chr12: 113554293–113554341 – – –S1503 chr17: 9443256–9443316 – – –S92I chr19: 44049878–44049927 – – –S592II chr19: 44049787–44049836 – – –2Nb chr6: 40151946–40151995 LTR10B1 ERV1 LTR9H chr4: 49630288–49630337 – – –CBE10d Un_gl000220: 101981–102031 (CCTTG)n repeat – –aClone names, as originally reported by el-Deiry et al. (1992).www.frontiersin.org March 2012 | Volume 3 | Article 40 | 1General Commentarypublished: 20 March 2012doi: 10.3389/fgene.2012.00040

p53 binding sites in transposons

Tomasz Zemojtel

Martin Vingron

Frontiers - Publisher Connector

P53 Binding Sites in Transposons

Crossref

Frontiers in Genetics

A commentary on
Definition of a consensus binding site for 
p53
by el-Deiry, W. S., Kern, S. E., Pietenpol, J. 
A., Kinzler, K. W., and Vogelstein, B. (1992). 
Nat. Genet. 1, 45–49.
Repeated regions of the genome harbor more 
functional information than commonly 
assumed. Two decades ago, a highly influ-
ential paper describing the consensus bind-
ing 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-spe-
cific (Jegga et al., 2008), suggesting a remark-
able 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 retro-
viral 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), high-
lighting the role of transposition in the emer-
gence 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 fami-
lies, 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-com-
plexity repeat.
In summary, the original work of el-
Deiry et al. (1992) published 20 years ago 
already contained evidence for the involve-
ment of transposable elements in spread-
ing species-specific p53 binding sites. This 
raised the question: how many more gems 
are hidden in previously generated data sets?
RefeRences
Cui, F., Sirotin, M. V., and Zhurkin, V. B. (2011). Impact 
of Alu repeats on the evolution of human p53 binding 
sites. Biol. Direct 6, 2.
el-Deiry, W. S., Kern, S. E., Pietenpol, J. A., Kinzler, K. W., 
and Vogelstein, B. (1992). Definition of a consensus 
binding site for p53. Nat. Genet. 1, 45–49.
Feschotte, C. (2008). Transposable elements and the 
evolution of regulatory networks. Nat. Rev. Genet. 
9, 397–405.
Harris, C. R., Dewan, A., Zupnick, A., Normart, R., 
Gabriel, A., Prives, C., Levine, A. J., and Hoh, J. (2009). 
p53 responsive elements in human retrotransposons. 
Oncogene 28, 3857–3865.
Jegga, A. G., Inga, A., Menendez, D., Aronow, B. J., and 
Resnick, M. A. (2008). Functional evolution of the 
p53 regulatory network through its target response 
elements. Proc. Natl. Acad. Sci. U.S.A. 105, 944–949.
Schmidt, D., Schwalie, P. C., Wilson, M. D., Ballester, B., 
Gonçalves, A., Kutter, C., Brown, G. D., Marshall, A., 
Flicek, P., and Odom, D. T. (2012). Waves of retro-
transposon expansion remodel genome organization 
and CTCF binding in multiple mammalian lineages. 
Cell 148, 335–348.
Wang, T., Zeng, J., Lowe, C. B., Sellers, R. G., Salama, S. 
R., Yang, M., Burgess, S. M., Brachmann, R. K., and 
Haussler, D. (2007). Species-specific endogenous ret-
roviruses shape the transcriptional network of the 
human tumor suppressor protein p53. Proc. Natl. 
Acad. Sci. U.S.A. 104, 18613–18618.
Zemojtel, T., Kielbasa, S. M., Arndt, P. F., Chung, H. R., and 
Vingron, M. (2009). Methylation and deamination of 
CpGs generate p53-binding sites on a genomic scale. 
Trends Genet. 25, 63–66.
Received: 22 February 2012; accepted: 01 March 2012; 
published online: 20 March 2012.
Citation: Zemojtel T and Vingron M (2011) p53 bind-
ing sites in transposons. Front. Gene. 3:40. doi: 10.3389/
fgene.2012.00040
This article was submitted to Frontiers in Evolutionary and 
Population Genetics, a specialty of Frontiers in Genetics.
Copyright © 2011 Zemojtel and Vingron. This is an open-
access article distributed under the terms of the Creative 
Commons Attribution Non Commercial License, which 
permits non-commercial use, distribution, and reproduc-
tion in other forums, provided the original authors and 
source are credited.
p53 binding sites in transposons
Tomasz Zemojtel* and Martin Vingron
Department of Computational Molecular Biology, Max-Planck-Institute for Molecular Genetics, Berlin, Germany
*Correspondence: zemojtel@molgen.mpg.de
Table 1 | Characterization of 20 sequences reported by el-Deiry et al. (1992).
Clonea Genomic location (hg19) Name Family Class
s57 chr13: 114536915–114536965 – – –
N22 chr11: 44182113–44182162 – – –
11A2 chr14: 100093893–100093943 – – –
W211 chr6: 116275323–116275368  L2a L2 LINE
W7B2 chr13: 52641535–52641585 MER61E ERV1 LTR
3H chr2: 191494065–191494114 HSMAR2 TcMar-Mariner DNA
8A chr4: 15767109–15767147 L2a L2 LINE
532 chr6: 170765704–170765758 – – –
64A2 chr6: 88193436–88193496 HERVIP10FH ERV1 LTR
W7A1 chr7: 22821881–22821930 – – –
S61 chr2: 32539190–32539238 L1ME3B L1 LINE
1183 chr10: 121965614–121965661 – – –
N42 chr7: 47737939–47737989 – – –
S201 chr12: 113554293–113554341 – – –
S1503 chr17: 9443256–9443316 – – –
S92I chr19: 44049878–44049927 – – –
S592II chr19: 44049787–44049836 – – –
2Nb chr6: 40151946–40151995 LTR10B1 ERV1 LTR
9H chr4: 49630288–49630337 – – –
CBE10d Un_gl000220: 101981–102031 (CCTTG)n repeat – –
aClone names, as originally reported by el-Deiry et al. (1992).
www.frontiersin.org March 2012 | Volume 3 | Article 40 | 1
General Commentary
published: 20 March 2012
doi: 10.3389/fgene.2012.00040


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