CHICKEN OVALBUMIN UPSTREAM PROMOTER TRANSCRIPTION FACTOR (COUP-TF) - EXPRESSION DURING MOUSE EMBRYOGENESIS

Members of the steroid/thyroid hormone receptor superfamily such as TR , RAR, RXR and VDR are known to play important roles in regulation of gene expression during development, differentiation and homeostasis. C OUP-TFs are orphan members of this superfamily of nuclear receptors an d have been shown to negatively regulate the ability of these nuclear receptors to transactivate target genes. Two different mechanisms are implicated in this repression. First, COUP-TFs bind to AGGTCA direct r epeats and palindromes with various spacings, which include response e lements for TR, RAR, RXR and VDR, allowing for direct competition of C OUP-TFs for the response elements. Second, COUP-TFs can heterodimerize with RXRs, the essential cofactor for effective binding of VDR, TRs a nd RARs to their cognate response elements. The physiological signific ance of this negative effect of COUP-TF on the activity of these recep tors has been analyzed. Detection of COUP-TF transcripts during mouse development reveal discrete spatial and temporal expression domains co nsistent with COUP-TFs being involved in regulation of gene expression during embryo-genesis. Transcripts are localized within discrete regi ons of the central and peripheral nervous system including the inner e ar. In addition, COUP-TFs are found in many tissues including testes, ovary, prostate, skin, kidney, lung, stomach, intestine, pancreas and salivary gland. Some of these expression domains colocalize with those of TR, RAR, and RXR. The simultaneous expresson of these genes raise the possibility that COUP-TFs can act as negative regulatory factors d uring development and differentiation.