Identification of altered DNA-protein interactions at the lamin A proximalpromoter in quiescent hepatocytes

The nuclear lamina of differentiated cells is composed of A-type and B-type lamins. The expression of the A-type lamins has been shown to be primarily under transcriptional control in proliferating cells. In order to gain ins ights into the factors involved in downregulation of the promoter in quiesc ent cells, we have compared the DNA-protein interactions at the rat lamin A proximal promoter in fetal (dividing) hepatocytes and adult (quiescent) he patocytes by DNase I footprinting analysis, electrophoretic mobility shift assays and UV crosslinking experiments. We have identified proteins from ad ult hepatocyte nuclear extracts that are bound to sequences within 28 bp do wnstream of the transcription initiation site (62 and 48 kDa proteins) and within 20 bp upstream of the initiation site (54 kDa protein), which may fu nction as transcriptional repressors of the lamin A proximal promoter.