SP1 ELEMENTS PROTECT A CPG ISLAND FROM DE-NOVO METHYLATION

ANIMAL somatic cell DNA is characterized by a bimodal pattern of methy lation: tissue-specific genes are methylated in most cell types wherea s housekeeping genes have 5' CpG islands which are constitutively unme thylated(1,2). Because methyl moieties derived from the gametes are er ased in the morula and early blastula(3), this profile must be re-esta blished in every generation; this is apparently accomplished by a wave of non-CpG island de novo methylation that occurs at implantation(4). Using transfection into embryonic stem cells and transgenic mice as a model system, we now show that Sp1 elements play a key role in protec ting a CpG island in the adenine phosphoribosyltransferase (APRT) gene from de novo methylation. This recognition mechanism represents a cri tical step in embryogenesis; as it is responsible for setting up the c orrect genome methylation pattern which, in turn, is involved in regul ating basal gene expression in the organism(5).