The COUP-TFs compose a family of functionally related transcription factors

The chicken ovalbumin upstream promoter transcription factors (COUP-TFs) are members of the steroid/thyroid hormone receptor superfamily and function in transcriptional regulation of a wide variety of genes. The COUP-TFs purified from HeLa nuclear extract by COUP-affinity chromatography are composed of multiple M(r) forms. The Low M(r) COUP-TFs (43,000, 44,000, 46,000, and 47,000 M(r)) produce a relatively fast migrating complex (C1) with DNA in electrophoresis mobility shift assays, while the high M(r) forms (66,000, 68,000, 72,000, and 74,000 M(r)) produce a slower migrating (C2) complex. The high M(r) COUP-TFs were purified by gel filtration chromatography and independently formed the C2 DNA complex, probably acting as dimers. The high M(r) forms are indistinguishable from the low M(r) COUP-TFs in DNA binding and in enhancement of in vitro transcription from the ovalbumin promoter. The finding of multiple COUP-TF forms led us to clone a second low M(r) COUP-TF, "COUP-TF2." The COUP-TF2 sequence has very strong homology with COUP-TF1. The N-termini of COUP-TF1 and COUP-TF2 are least similar, but both contain glutamine-rich and proline-rich motifs, putative activation domains.