Strategy for detecting cellular transcripts promoted by human endogenous long terminal repeats: Identification of a novel gene (CDC4L) with homology to yeast CDC4

Several families of repetitive sequences related to integrated retroviruses have been identified in the human genome. The largest of these families, the RTVL-H family, has close to 1000 members in addition to a similar number of solitary long terminal repeats (LTRs) dispersed on all chromosomes. Previous work has shown that the expression of genomic RTVL-H elements is driven by their LTRs and that some LTRs can promote expression of a reporter gene. These observations suggest that some endogenous RTVL-HLTRs may naturally regulate the transcription of adjacent cellular genes or that rearrangements involving these elements may cause aberrant gene expression. To investigate this possibility, we have used a differential screening strategy to identify chimeric cDNA clones derived from LTR-promoted transcripts. Here we report the identification and analysis of four such clones isolated from an NTera2D1 (teratocarcinoma) cDNA library. Two of the clones, AF-1 and AF-2, contain termination codons in all reading frames. Another clone, AF-4, contains LTR sequences linked in the genome to a CpG island. The fourth clone, AF-3, contains an 862-bp open reading frame representing part of a novel gene (CDC4L) with homology to the yeast cell division cycle gene CDC4. These findings indicate that RTVL-H elements may be involved in the regulation of diverse cellular transcripts in human cells.