Table 5C-1. Mobile Elements Found to be Exapted as cis-Regulatory Control Sites in Animals


Locus or system

Mobile Element


Drosophila simulans

Cyp6g1 (encoding a cytochrome P450) – insecticide resistance

Doc DNA transposon


(Schlenke and Begun 2004)

Drosophila melanogaster

Tissue-specific expression of the insecticide resistance gene Cyp6g1.

Cis-regulatory elements in the Accord retrotransposon

(Daborn, Yen et al. 2002; Chung, Bogwitz et al. 2007)


105 highly conserved sequences from amphioxus through humans not associated with protein coding sequences.

Ancient SINE family AmnSINE1, (Amniota SINE1) present in mammals and birds; AmnSINE1 chimeric structure of 5S rRNA and a tRNA-derived SINE, related to five tRNA-derived SINE families in the coelacanth, dogfish shark, hagfish, and amphioxus genomes. We collectively name DeuSINE (Deuterostomia SINE) superfamily.

(Nishihara, Smit et al. 2006)

Indonesian coelacanth, Latimeria menadoensis

Previously unknown SINE retroposon family active in Sarcopterygii (lobe-finned fishes and terrestrial vertebrates) in Silurian period >410 million years ago

Mouse enhancer assay recapitulates multiple aspects of Isl1 expression patterns. A >200-base-pair ultraconserved region, 100% identical in mammals, and 80% identical to the coelacanth SINE, contains a 31-amino-acid-residue alternatively spliced exon of the messenger RNA processing gene PCBP2.

(Bejerano, Lowe et al. 2006)

Mammals (placentals, marsupials, monotremes), but not other vertebrates

Proopiomelanocortin (POMC) locus

Ancient exaptation of a CORE-SINE into highly conserved neuronal enhancer nPE2.

(Santangelo, de Souza et al. 2007)



16 Pax6 binding sites (eye and CNS development factor)

B1 SINE elements

(Zhou, Zheng et al. 2000)

Homo sapiens

Novel PAX6 binding sites

Alu SINE repeats at 3 loci

(Zhou, Zheng et al. 2002)


Lama3 transcript, stimulated by transcription factor USF (upstream stimulatory factor)

B2 SINE elements provide RNA polymerase II promoter

(Ferrigno, Virolle et al. 2001)


CTCF (11-zinc finger protein or CCCTC-binding transcription factor) networks; transcriptional regulation, insulator activity, V(D)J joining and chromatin formatting

Fossilized repeat elements flank conserved CTCF-binding regions, indicating retrotransposon expansions hundreds MYA; repeat-driven dispersal of CTCF binding is ancient and still highly active

(Schmidt, Schwalie et al. 2012)


FGF8 (fibroblast growth factor 8)

AmnSINE1 (AS071) enhancer recapitulates FGF8 expression in developing forebrain, diencephalon and hypothalamus

(Sasaki, Nishihara et al. 2008)


SINE 390 kbp upstream of Satb2

 AmnSINE1 (AS021) SINE displays specific enhancer activity in developing cerebral cortex


(Tashiro, Teissier et al. 2011)

Rodents, humans

Anti-apoptotic locus NAIP (BIRC1)

Repeated recruitment of LTR retrotransposons as promoters during mammalian evolution; 5' flanking regions of IAP family as group, in both human and mouse, enriched for LTR insertions

(Romanish, Lock et al. 2007)

Homo sapiens

Novel NAIP isoform

Alu SINE element start site

(Romanish, Nakamura et al. 2009)

Primates (baboon, human)

Primate beta3GAL-T5 colon expression

ERV1 LTR promoter

(Dunn, Medstrand et al. 2003; Dunn, van de Lagemaat et al. 2005)

Homo sapiens

enhancer in last intron of human CD8 alpha locus

Alu SINE-containing, T-cell-specific enhancer

(Hambor, Mennone et al. 1993)

Homo sapiens

Down syndrome critical region 4 (DSCR4) and DSCR8 loci

ERV1 LTR acts as a bidirectional promoter

(Dunn, Romanish et al. 2006)

Mouse, human

REST (RE1-Silencing Transcription Factor) targets many neural genes in preimplantation embryo and CNS by cognate DNA motif, RE1 (Repressor Element 1).

1301 and 997 RE1s in human and mouse genomes, respectively, >40% are novel (many LINE1, LINE2, Alu SINE in human genome); weak RE1 elements in hERV.

(Johnson, Gamblin et al. 2006; Johnson, Samuel et al. 2009)


Estrogen Receptor α (ERα) response loci

MIR (mammalian interspersed repeat) SINEs 15-25% of TEs conserved between human and mouse; include targets ERα, such as GREB1, RARα. TAP/SEC14L2, GLUT1/SLC2A1 (ERα mediated response to hypoxia), Anxa6, Fyn, CA12, CYP1B1, KRT13 and PRKACA

(Testori, Caizzi et al. 2012)

zebrafish (Danio rerio)

180 p53 responsive loci; human orthologs contribute neuronal morphogenesis, axonogenesis, synaptic transmission and regulation of programmed cell death

EnSpmN6_DR non-autonomous DNA transposon

(Micale, Loviglio et al. 2012)

Homo sapiens

p53 regulon

1,509 of ~ 319,000 human ERV LTR regions have a near-perfect p53 DNA binding site; LTR10 and MER61 families particularly enriched; primate-specific

(Wang, Zeng et al. 2007)

Homo sapiens and mouse

c-Myc regulatory subnetwork

Thousands TEs bound by c-Myc; 816-4564 contain canonical c-Myc binding motifs; c-Myc binding sites over-represented among ancient families LINE2 and MIR; loci with TE-derived c-Myc binding sites co-expressed with each other and with c-Myc. Conserved fragments of MIR and LINE2 transposable elements in intergenic regions within the mouse and human genomes

(Wang, Bowen et al. 2009) (Silva, Shabalina et al. 2003)

Eutherian mammals

Endometrial expression in placental mammals

13% of 1,532 endometrial-expressed loci are within 200 kb of a Eutherian-specific MER20 transposable element; these elements have epigenetic signatures of enhancers, insulators and repressors and directly bind transcription factors essential for pregnancy to regulate expression in response to progesterone and cAMP.

(Lynch, Leclerc et al. 2011)




Bejerano, G., C. B. Lowe, et al. (2006). "A distal enhancer and an ultraconserved exon are derived from a novel retroposon." Nature 441(7089): 87-90.

Chung, H., M. R. Bogwitz, et al. (2007). "Cis-regulatory elements in the Accord retrotransposon result in tissue-specific expression of the Drosophila melanogaster insecticide resistance gene Cyp6g1." Genetics 175(3): 1071-1077.

Daborn, P. J., J. L. Yen, et al. (2002). "A single p450 allele associated with insecticide resistance in Drosophila." Science 297(5590): 2253-2256.

Dunn, C. A., P. Medstrand, et al. (2003). "An endogenous retroviral long terminal repeat is the dominant promoter for human beta1,3-galactosyltransferase 5 in the colon." Proc Natl Acad Sci U S A 100(22): 12841-12846.

Dunn, C. A., M. T. Romanish, et al. (2006). "Transcription of two human genes from a bidirectional endogenous retrovirus promoter." Gene 366(2): 335-342.

Dunn, C. A., L. N. van de Lagemaat, et al. (2005). "Endogenous retrovirus long terminal repeats as ready-to-use mobile promoters: the case of primate beta3GAL-T5." Gene 364: 2-12.

Ferrigno, O., T. Virolle, et al. (2001). "Transposable B2 SINE elements can provide mobile RNA polymerase II promoters." Nat Genet 28(1): 77-81.

Hambor, J. E., J. Mennone, et al. (1993). "Identification and characterization of an Alu-containing, T-cell-specific enhancer located in the last intron of the human CD8 alpha gene." Mol Cell Biol 13(11): 7056-7070.

Johnson, R., R. J. Gamblin, et al. (2006). "Identification of the REST regulon reveals extensive transposable element-mediated binding site duplication." Nucleic Acids Res 34(14): 3862-3877.

Johnson, R., J. Samuel, et al. (2009). "Evolution of the vertebrate gene regulatory network controlled by the transcriptional repressor REST." Mol Biol Evol 26(7): 1491-1507.

Lynch, V. J., R. D. Leclerc, et al. (2011). "Transposon-mediated rewiring of gene regulatory networks contributed to the evolution of pregnancy in mammals." Nat Genet 43(11): 1154-1159.

Micale, L., M. N. Loviglio, et al. (2012). "A fish-specific transposable element shapes the repertoire of p53 target genes in zebrafish." PLoS One 7(10): e46642.

Nishihara, H., A. F. Smit, et al. (2006). "Functional noncoding sequences derived from SINEs in the mammalian genome." Genome Res 16(7): 864-874.

Romanish, M. T., W. M. Lock, et al. (2007). "Repeated recruitment of LTR retrotransposons as promoters by the anti-apoptotic locus NAIP during mammalian evolution." PLoS Genet 3(1): e10.

Romanish, M. T., H. Nakamura, et al. (2009). "A novel protein isoform of the multicopy human NAIP gene derives from intragenic Alu SINE promoters." PLoS One 4(6): e5761.

Santangelo, A. M., F. S. de Souza, et al. (2007). "Ancient exaptation of a CORE-SINE retroposon into a highly conserved mammalian neuronal enhancer of the proopiomelanocortin gene." PLoS Genet 3(10): 1813-1826.

Sasaki, T., H. Nishihara, et al. (2008). "Possible involvement of SINEs in mammalian-specific brain formation." Proc Natl Acad Sci U S A 105(11): 4220-4225.

Schlenke, T. A. and D. J. Begun (2004). "Strong selective sweep associated with a transposon insertion in Drosophila simulans." Proc Natl Acad Sci U S A 101(6): 1626-1631.

Schmidt, D., P. C. Schwalie, et al. (2012). "Waves of retrotransposon expansion remodel genome organization and CTCF binding in multiple mammalian lineages." Cell 148(1-2): 335-348.

Silva, J. C., S. A. Shabalina, et al. (2003). "Conserved fragments of transposable elements in intergenic regions: evidence for widespread recruitment of MIR- and L2-derived sequences within the mouse and human genomes." Genet Res 82(1): 1-18.

Tashiro, K., A. Teissier, et al. (2011). "A Mammalian Conserved Element Derived from SINE Displays Enhancer Properties Recapitulating Satb2 Expression in Early-Born Callosal Projection Neurons." PLoS One 6(12): e28497.

Testori, A., L. Caizzi, et al. (2012). "The role of transposable elements in shaping the combinatorial interaction of transcription factors." BMC Genomics 13(1): 400.

Wang, J., N. J. Bowen, et al. (2009). "A c-Myc regulatory subnetwork from human transposable element sequences." Mol Biosyst 5(12): 1831-1839.

Wang, T., J. Zeng, et al. (2007). "Species-specific endogenous retroviruses shape the transcriptional network of the human tumor suppressor protein p53." Proc Natl Acad Sci U S A 104(47): 18613-18618.

Zhou, Y., J. B. Zheng, et al. (2000). "A novel Pax-6 binding site in rodent B1 repetitive elements: coevolution between developmental regulation and repeated elements?" Gene 245(2): 319-328.

Zhou, Y. H., J. B. Zheng, et al. (2002). "Novel PAX6 binding sites in the human genome and the role of repetitive elements in the evolution of gene regulation." Genome Res 12(11): 1716-1722.