Wang, T. et al. Species-specific endogenous retroviruses shape the transcriptional network of the human tumor suppressor protein p53. Proc. Natl Acad. Sci. USA 104, 18613-18618

Center for Biomolecular Science and Engineering, and Howard Hughes Medical Institute, University of California, Santa Cruz, CA 95064, USA.
Proceedings of the National Academy of Sciences (Impact Factor: 9.81). 12/2007; 104(47):18613-8. DOI: 10.1073/pnas.0703637104
Source: PubMed

ABSTRACT The evolutionary forces that establish and hone target gene networks of transcription factors are largely unknown. Transposition of retroelements may play a role, but its global importance, beyond a few well described examples for isolated genes, is not clear. We report that LTR class I endogenous retrovirus (ERV) retroelements impact considerably the transcriptional network of human tumor suppressor protein p53. A total of 1,509 of approximately 319,000 human ERV LTR regions have a near-perfect p53 DNA binding site. The LTR10 and MER61 families are particularly enriched for copies with a p53 site. These ERV families are primate-specific and transposed actively near the time when the New World and Old World monkey lineages split. Other mammalian species lack these p53 response elements. Analysis of published genomewide ChIP data for p53 indicates that more than one-third of identified p53 binding sites are accounted for by ERV copies with a p53 site. ChIP and expression studies for individual genes indicate that human ERV p53 sites are likely part of the p53 transcriptional program and direct regulation of p53 target genes. These results demonstrate how retroelements can significantly shape the regulatory network of a transcription factor in a species-specific manner.

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    • "us , our results support a new , elegantly simple model of molecular evolution in which new functions arise more or less at random in the genome , with little regard to repeat status or repeat family . This is at variance with the conclusions of studies based on biochemical definitions of function , which detect massive enrichment of LTR repeats ( Wang et al . 2007 ; Jacques et al . 2013 ; Chuong et al . 2013 ; Thurman et al . 2012 ) . The most parsimonious explanation for these divergent findings is that there exists in the genome a large number of biochemically active LTRs that have little or no biological function . Another possible explanation is that the biochemically - based studies examined"
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