DIFFERENTIATION-SPECIFIC ELEMENT - A CIS-ACTING DEVELOPMENTAL SWITCH REQUIRED FOR THE SUSTAINED TRANSCRIPTIONAL EXPRESSION OF THE ANGIOTENSINOGEN GENE DURING HORMONAL-INDUCED DIFFERENTIATION OF 3T3-L1 FIBROBLASTS TO ADIPOCYTES

The gene encoding angiotensinogen, the glycoprotein precursor for the vasopressor angiotensin II, is under coordinate tissue-specific, developmental, and hormonal regulation. We show here that the irreversible, developmentally regulated increase in angiotensinogen gene expression during the hormonal (dexamethasone, insulin, and isobutylmethylxanthine) differentiation of fibroblast-like 3T3-L1 cells into adipocytes is mediated by a 14-base pair cis-acting element located at -1000 in the 5'-flanking region of the gene. The sequence of this differentiation-specific element (DSE) is similar to sites that bind the homeotic and pou class of transcription factors found in the promoters of other genes known to be regulated during differentiation. Furthermore, we show that there are several high affinity DSE-specific binding proteins present in preadipocyte nuclear extracts that are competed with known homeotic and pou transcription factor DNA binding sequences. Thus the DSE appears to serve as a developmental switch for the expression of the angiotensinogen gene during the differentiation of fibroblasts to adipocytes and may be a binding site for one or more of the pou-homeodomain class of transcription factors.