Studies on the transcriptional regulation of Lefty1 during neuronal differentiation of P19 embryonic carcinoma cells

Abstract

Stem cell division should be tightly controlled for a proper balance between self-renewal and differentiation. It is recently known that some types of stem cells have to undergo minimal rounds of cell division in order to turn on expression of a set of genes for differentiation. Here, I searched for genes of which the expression is controlled in a cell-division-dependent manner during neuronal differentiation of P19 embryonic carcinoma cells. I identified three candidate genes, Lefty1, Msi2, and Prtg of which the expressions were upregulated during the retinoic acid-induced neurogenesis in P19 cells. Their expressions were induced by RA in a delayed manner, and such induction was significantly dampened by cell cycle blocking drugs such as thymidine and RO3306. I defined a domain within the Lefty1 promoter sequence that is responsible for cell-division-dependent activation. These results provide a clue on mechanisms how gene expression is controlled by cell division for neuronal differentiation.