Analyses on the degradation of Hes, a transcription factor, regulates timings of cellular differentiation

点击翻译按钮获取中文摘要

The basic helix-loop-helix (bHLH) gene Hes is expressed in an oscillatory manner and regulates the differentiation timings at developmental stages. Oscillatory expression of Hes depends on rapid degradation of the gene products, but the precise mechanisms of both how the degradation of Hes protein are regulated and how the timings of cell differentiation are regulated by Hes oscillation remain unclear. First, we found that some lysine residues are essential not only for the instability of Hes7 protein but also for the transcriptional repressor activity. Second, we found that expression of Hes1 oscillates in mouse embryonic stem (ES) cells every 3-5 hours. ES cells expressing low and high levels of Hes1 tended to differentiate into neural and mesodermal cells, respectively. Furthermore, inactivation of Hes1 facilitated neural differentiation more uniformly at earlier time. We revealed that the cyclic expression of Hes1 gene contributes to heterogeneous differentiation of homogenous ES cell populations.