Methods and compositions are provided for increasing the expression of a gene of interest in a plant by co-expressing the gene of interest with a p21 polynucleotide. The gene of interest can be endogenous or heterologous to the plant. Further provided are plants, such as tobacco plants, comprising a heterologous p21 polynucleotide. Co-expression of the p21 polynucleotide with a gene of interest in the plant increases the expression of the gene of interest when compared to a control plant. Accordingly, p21 co-expression can increase the expression of genes of interest encoding proteins such as defense proteins, enzymes, signaling proteins, reporter proteins, antibodies and fragments thereof, growth factors, cell surface receptor molecules, seed storage proteins, and fungicides in a plant.