Transcription factor CREM coordinates the timing of hepatocyte proliferation in the regenerating liver

The liver regenerates upon partial hepatectomy (PH) as terminally different iated hepatocytes undergo a tremendous proliferative process. CREM gene exp ression is powerfully induced during liver regeneration. We show that cell proliferation is significantly reduced upon PH in CREM-/- mice. There is a reduction in DNA synthesis, in the number of mitosis and of phosphorylated histone H3-positive cells. The post-PH proliferation peak is delayed by 10 hr, indicating an altered hepatocyte cell cycle. Expression of cyclins A, B , D1, E, and cdc2, of c-fos and tyrosine aminotransferase is deregulated. C REM mutation results in delayed S-phase entry, impairing the synchronizatio n of proliferation.