Isolation of a cDNA encoding human Rev-ErbA alpha: transcription from the noncoding DNA strand of a thyroid hormone receptor gene results in a related protein that does not bind thyroid hormone

A cDNA encoding Rev-ErbA alpha, a member of the thyroid/steroid hormone receptor superfamily, has been isolated from a human fetal skeletal muscle library. This cDNA contains 269 consecutive base pairs identical to a region of a human c-erbA alpha-2 cDNA, but the respective long open reading frames utilize this nucleotide sequence in opposite orientations. Thus, human Rev-ErbA alpha (hRev) is derived from opposite-strand transcription of the c-erbA alpha genomic locus. mRNA encoding hRev was detected in human skeletal muscle by Northern analysis. Comparison of hRev and Rev-ErbA (rRev) reveals 99% identity in the putative DNA-binding and "ligand-binding" (carboxy-terminal) domains. hRev does not bind thyroid hormone (T3), as has also been found for its rat homolog. Interestingly, the human and rat Rev-ErbA alpha cDNAs are dissimilar at their 5' ends, corresponding to the first exon that we have identified in the rat gene. The conservation of the bidirectionally transcribed regions of c-erbA alpha-2 and Rev-ErbA alpha in human and rat suggests that this unusual genomic arrangement has an important function, perhaps related to the regulation of gene expression.