The impact of CpG island on defining transcriptional activation of the mouse L1 retrotransposable elements.
BACKGROUND
L1 retrotransposable elements are potent insertional mutagens responsible for the generation of genomic variation and diversification of mammalian genomes, but reliable estimates of the numbers of actively transposing L1 elements are mostly nonexistent. While the human and mouse genomes contain comparable numbers of L1 elements, several phylogenetic and L1Xplore analyses in the mouse genome suggest that 1,500-3,000 active L1 elements currently exist and that they are still expanding in the genome. Conversely, the human genome contains only 150 active L1 elements. In addition, there is a discrepancy among the nature and number of mouse L1 elements in L1Xplore and the mouse genome browser at the UCSC and in the literature. To date, the reason why a high copy number of active L1 elements exist in the mouse genome but not in the human genome is unknown, as are the potential mechanisms that are responsible for transcriptional activation of mouse L1 elements.


RESULTS
We analyzed the promoter sequences of the 1,501 potentially active mouse L1 elements retrieved from the GenBank and L1Xplore databases and evaluated their transcription factors binding sites and CpG content. To this end, we found that a substantial number of mouse L1 elements contain altered transcription factor YY1 binding sites on their promoter sequences that are required for transcriptional initiation, suggesting that only a half of L1 elements are capable of being transcriptionally active. Furthermore, we present experimental evidence that previously unreported CpG islands exist in the promoters of the most active T(F) family of mouse L1 elements. The presence of sequence variations and polymorphisms in CpG islands of L1 promoters that arise from transition mutations indicates that CpG methylation could play a significant role in determining the activity of L1 elements in the mouse genome.


CONCLUSIONS
A comprehensive analysis of mouse L1 promoters suggests that the number of transcriptionally active elements is significantly lower than the total number of full-length copies from the three active mouse L1 families. Like human L1 elements, the CpG islands and potentially the transcription factor YY1 binding sites are likely to be required for transcriptional initiation of mouse L1 elements.
Lee
Sung-Hun
SH
The John Curtin School of Medical Research, Australian National University, Canberra, Australia.
Cho
Soo-Young
SY
Shannon
M Frances
MF
Fan
Jun
J
Rangasamy
Danny
D
D000818:Animals; D001665:Binding Sites; D050677:Core Binding Factor Alpha 3 Subunit / Q000378:metabolism; D018899:CpG Islands; D006801:Humans; D051379:Mice; D016254:Mutagenesis, Insertional; D018626:Retroelements; D015533:Transcriptional Activation; D050986:YY1 Transcription Factor / Q000378:metabolism
D050677:Core Binding Factor Alpha 3 Subunit; D018626:Retroelements; C493730:Runx3 protein, mouse; D050986:YY1 Transcription Factor; C494699:Yy1 protein, mouse