Wang T, Zeng J, Lowe CB, Sellers RG, Salama SR, Yang M 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: 9.67). 12/2007; 104(47):18613-8. DOI: 10.1073/pnas.0703637104
Source: PubMed


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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Available from: Shawn Burgess, Nov 05, 2015
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    • "During embryonic development LTR REs operate as alternative promotors, enhancers [13–15, 92], first exons for a subset of host genes [87], and as targets of transcription factors [93]. Retroelements are even able to serve host functions for genes over longer distances as the example of the human ERV-9 demonstrates [94]. "
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    ABSTRACT: Background LTR retroelements (LTR REs) constitute a major group of transposable elements widely distributed in eukaryotic genomes. Through their own mechanism of retrotranscription LTR REs enrich the genomic landscape by providing genetic variability, thus contributing to genome structure and organization. Nonetheless, transcriptomic activity of LTR REs still remains an obscure domain within cell, developmental, and organism biology. Results Here we present a first comparative analysis of LTR REs for anuran amphibians based on a full depth coverage transcriptome of the European pool frog, Pelophylax lessonae, the genome of the African clawed frog, Silurana tropicalis (release v7.1), and additional transcriptomes of S. tropicalis and Cyclorana alboguttata. We identified over 1000 copies of LTR REs from all four families (Bel/Pao, Ty1/Copia, Ty3/Gypsy, Retroviridae) in the genome of S. tropicalis and discovered transcripts of several of these elements in all RNA-seq datasets analyzed. Elements of the Ty3/Gypsy family were most active, especially Amn-san elements, which accounted for approximately 0.27% of the genome in Silurana. Some elements exhibited tissue specific expression patterns, for example Hydra1.1 and MuERV-like elements in Pelophylax. In S. tropicalis considerable transcription of LTR REs was observed during embryogenesis as soon as the embryonic genome became activated, i.e. at midblastula transition. In the course of embryonic development the spectrum of transcribed LTR REs changed; during gastrulation and neurulation MuERV-like and SnRV like retroviruses were abundantly transcribed while during organogenesis transcripts of the XEN1 retroviruses became much more active. Conclusions The differential expression of LTR REs during embryogenesis in concert with their tissue-specificity and the protein domains they encode are evidence for the functional roles these elements play as integrative parts of complex regulatory networks. Our results support the meanwhile widely accepted concept that retroelements are not simple “junk DNA” or “harmful genomic parasites” but essential components of the transcriptomic machinery in vertebrates. Electronic supplementary material The online version of this article (doi:10.1186/1471-2164-15-626) contains supplementary material, which is available to authorized users.
    BMC Genomics 07/2014; 15(1):626. DOI:10.1186/1471-2164-15-626 · 3.99 Impact Factor
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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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    ABSTRACT: Little is known about novel genetic elements that drove the emergence of anthropoid primates. We exploited the sequencing of the marmoset genome to identify 23,849 anthropoid-specific constrained (ASC) regions, and confirmed their robust functional signatures. 99.7% of ASC basepairs were noncoding, suggesting that novel anthropoid functional elements were overwhelmingly cis-regulatory. ASCs were highly enriched in loci associated with fetal brain development, motor coordination, neurotransmission and vision, thus providing a large set of candidate elements for exploring the molecular basis of hallmark primate traits. We validated ASC192 as a primate-specific enhancer in proliferative zones of the developing brain. Unexpectedly, transposable elements (TEs) contributed to >56% of ASCs, and almost all TE families showed functional potential similar to that of non-repetitive DNA. Three L1PA repeat-derived ASCs displayed coherent eye-enhancer function, thus demonstrating that the 'gene-battery' model of TE functionalization applies to enhancers in vivo. Our study provides fundamental insights into genome evolution and the origins of anthropoid phenotypes, and supports an elegantly simple new null model of TE exaptation.
    Genome Research 07/2014; Genome Res. 2014 Jul 20. pii: gr.168963.113.(pii: gr.168963.113.[Epub ahead of print]). DOI:10.1101/gr.168963.113 · 14.63 Impact Factor
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    • " al . 2011 ) . The readthrough transcription of a host gene locus initiated by a retrotransposon promoter might represent a first step in a process of transposon domestication that culminates with transposon - derived sequences used as regulatory elements for host gene expression ( Duhl et al . 1994 ; Peaston et al . 2004 ; Romanish et al . 2007 ; Wang et al . 2007 ; Feschotte 2008 ; Li et al . 2012 ) ."
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    ABSTRACT: Transposable elements (TEs) occupy a large fraction of metazoan genomes and pose a constant threat to genomic integrity. This threat is particularly critical in germ cells, as changes in the genome that are induced by TEs will be transmitted to the next generation. Small noncoding piwi-interacting RNAs (piRNAs) recognize and silence a diverse set of TEs in germ cells. In mice, piRNA-guided transposon repression correlates with establishment of CpG DNA methylation on their sequences, yet the mechanism and the spectrum of genomic targets of piRNA silencing are unknown. Here we show that in addition to DNA methylation, the piRNA pathway is required to maintain a high level of the repressive H3K9me3 histone modification on long interspersed nuclear elements (LINEs) in germ cells. piRNA-dependent chromatin repression targets exclusively full-length elements of actively transposing LINE families, demonstrating the remarkable ability of the piRNA pathway to recognize active elements among the large number of genomic transposon fragments.
    Genes & Development 06/2014; 28(13). DOI:10.1101/gad.240895.114 · 10.80 Impact Factor
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