Two subfamilies of murine retrotransposon ETn sequences.

Early transposon (ETn) elements are 5.7-kb retrotransposons found in the murine genome. We have sequenced large portions of two ETn elements that have apparently transposed within the DNA of a murine myeloma cell line, P3.26Bu4. One of the transposed ETn elements has 5' and 3' long terminal repeats (LTRs) that are exact duplicates of each other and has a 6-bp target site duplication. These results suggest that this element, which inserted into an immunoglobulin gamma 1 switch region, moved by a retrotransposition process. Our nucleotide sequences confirm that individual ETn elements are very similar to one another and lack open reading frames. However, the ETn sequences reported here and those previously described differ significantly near their 5' LTRs, including 200 bp of weak similarity and 240 bp of complete disparity. Southern hybridization analysis suggests that both subfamilies of ETn sequences are represented many times in the mouse genome. The possibility that the disparate sequences have a role in transposition by ETn elements is discussed.

DNA sequences near the site of reciprocal recombination between a c-myc oncogene and an immunoglobulin switch region.

The chromosomal translocations found in many B-cell tumors result in the joining of a c-myc oncogene with an immunoglobulin heavy chain switch region. This finding is striking because the natural function of switch regions is to mediate DNA rearrangements important to the maturation of immune responses. These normal switch rearrangements are probably mediated by specific enzymes. In this paper we report the isolation of the two reciprocal products of a recombination between a c-myc gene on murine chromosome 15 and an immunoglobulin switch region (S mu S gamma 2b) on chromosome 12. We have determined the sequences of these DNA molecules near the recombination sites and show that the recombination is nearly perfectly reciprocal, with a seven-nucleotide deletion. An examination of the sequences reported in this paper, and of sequences published by other authors, shows a correlation between the points of recombination for c-myc-S segment rearrangements and for normal heavy chain switches. We suggest that this correlation implies a role for switch recombination enzymes in creating substrates for the c-myc recombination. The c-myc gene also seems to share some limited homology to sequences thought to be important in heavy chain switching. Finally, we discuss a working model that accounts for some characteristics of c-myc-S segment recombinations. The model also suggests a mechanism for increased transcriptional activity of the rearranged c-myc oncogene in B-cell tumors.