REEXPRESSION OF RETINOIC ACID RECEPTOR (RAR)GAMMA OR OVEREXPRESSION OF RAR-ALPHA OR RAR-BETA IN RAR-GAMMA-NULL F9 CELLS REVEALS A PARTIAL FUNCTIONAL REDUNDANCY BETWEEN THE 3 RAR TYPES

Disruption of retinoic acid receptor (RAR)gamma in F9 embryonal carcin oma cells leads to aberrent differentiation and reduced activation of expression of several all-trans-retinoic acid (RA)-induced genes. We h ave analyzed the expression of several additional RA-responsive genes in RAR alpha- and RAR gamma-null F9 cells. The RA-induced activation o f Cdx1, Gap43, Stra4, and Stra6 was specifically impaired in RAR gamma -null cells, supporting the idea that each RAR magregulate distinct su bsets of target genes. To further investigate the role of RAR gamma in F9 cell differentiation, ''rescue'' cell lines reexpressing RAR gamma 2 or overexpressing either RAR alpha 1 or RAR beta 2 were established in RAR gamma-null cells. Reexpression of RAR gamma or overexpression of RAR alpha restored both target-gene activation and the differentiat ion potential. In contrast, overexpression of RAR beta only poorly res tored differentiation, although it could replace RAR gamma for the act ivation of target genes. Functional redundancy between the various RAR s is discussed.