CD3ζ/η/θ locus is colinear with and transcribed antisense to the gene encoding the transcription factor Oct-1

CD3ζ and η are signal-transducing components of the TCR and are derived from alternative splicing of transcripts from a single genetic locus that also encodes CD3θ. We have isolated two murine cDNA clones that appear to result from antisense transcription through CD3θ-specific exon 10 and CD3η- specific exon 9. The sequence of these clones shows no open reading frame. Northern analysis with single stranded probes confirms the existence of a ubiquitously expressed >12-kb polyadenylated mRNA antisense to CD3η. A 'genomic walk,' which extended 32 kb distal to murine CD3η exon 9, provided genomic DNA containing a more 5' portion of the antisense transcript. This probe identified two murine thymic cDNA with 91% sequence homology to the human transcription factor Oct-1. Five exons of murine Oct-1 map in an antisense orientation to the CD3ζ/η/θ locus on the cloned genomic sequences. The murine Oct-1 cDNA and exon 9 of CD3η hybridize to the same >12-kb mRNA. Similarly, human Oct-1 and previously characterized human genomic sequences homologous to murine CD3η exon 9 each hybridize to the same >15-kb human mRNA. Thus, the CD3ζ/η/θ and Oct-1 gene loci are partially overlapping and transcribed in opposite directions. The potential functional implications of these findings are discussed.