"Negative regulation of the mouse Aldolase A gene"

The expression of aldolase A L-type mRNA is in- increased creased in growth-arrested mouse NIH3T3 cells and re- remarkably markably down-regulated in actively proliferating cells. Treatment of proliferating cells with cycloheximide abolished the down-regulation of L-type mRNA expres- expression, sion, thus indicating that a protein factor acts as repres- repressor sor in proliferating cells. Transient transfection experi- experiments ments in NIH3T3 cells showed that a negative regulatory cis cis-element -(NRE) is involved in the modula- modulation tion of the transcriptional activity of the distal L pro- promoter. moter. The repressor, which is a protein of !97 kDa, binds the murine aldolase A NRE, revealing a much more intense DNA-protein complex in proliferating NIH3T3 cells than in serum-deprived cells. Mutations in the negative regulatory cis cis-element -showed that the GA- GArich rich motif is required for protein binding and silencer function. We conclude that the expression of L-type mRNA is modulated by the interaction between a cell cycle-dependent DNA-binding protein and the murine aldolase A NRE.