Rev-Erb A Alpha - Gene and Protein Structure

Gene and Protein Structure

Rev-erbα is transcribed from the opposite strand of the thyroid receptor α (c-erbAα) gene on chromosome 17, with a 269-nucleotide overlap between the two transcripts. The other mammalian isoform of the receptor, Rev-erbβ is encoded by another gene on chromosome 3. In addition, there is one non-mammalian homolog, the ecdysone-regulated gene E75, which is present in Drosophila and C. elegans. The Rev-erbα gene itself has multiple transcripts. Two promoters govern the expression of the Rev-erbα gene in human and rat, generating two mRNA isoforms. The full-length isoform encodes a 614-amino acid protein, while a second isoform is generated from an internal promoter and produces a protein that is shorter by 106 amino acids. Both Rev-erbα mRNA isoforms contain E-boxes as well as Rev-erbα response elements, which means that they can be regulated in a circadian manner by the BMAL and Rev-erba proteins. In fact, both transcripts exhibit rhythmic expression in serum-synchronized fibroblasts.

The Rev-erbα protein is structurally unique from other nuclear receptors, in that it lacks helix 12 (H12) in its ligand-binding domain, which is usually responsible for forming the ligand binding pocket in other nuclear receptors. In place of the missing H12, Rev-erbα displays a hydrophobic interface that binds the corepressor N-CoR, making it a potent transcriptional repressor. Interestingly, all members of the Rev-erb family bind heme, which may act as a ligand to regulate their transcriptional activity.