Isolation of retinoic acid-repressed genes from P19 embryonal carcinoma cells.

Retinoic acid (RA) plays a critical role in normal development, growth and differentiation by modulating the expression of target genes. Using substractive hybridization cloning, we isolated two cDNAs, whose corresponding mRNAs are repressed upon RA treatment of P19 embryonal carcinoma (EC) cells. The cDNAs correspond to the serine hydroxymethyltransferase (shmt) gene and the early transposon, ETnMG1. RA appears to reduce the stability of ETnMG1 transcript. We also report the sequence of two different isoforms of mouse SHMT. Since SHMT activity is increased when cells are stimulated to proliferate and during the S phase of the cell cycle, we suggest that repression of shmt expression is an important step in RA-induced cell growth arrest and differentiation.