TRANSCRIPTION FACTOR SP1 IS ESSENTIAL FOR EARLY EMBRYONIC-DEVELOPMENTBUT DISPENSABLE FOR CELL-GROWTH AND DIFFERENTIATION

Transcription factor Sp1 has been implicated in the expression of many genes. Moreover, it has been suggested that Sp1 is linked to the main tenance of methylation-free CpG islands, the cell cycle, and the forma tion of active chromatin structures. We have inactivated the mouse Sp1 gene. Sp1(-/-) embryos are retarded in development, show a broad rang e of abnormalities, and die around day 11 of gestation. In Sp1(-/-) em bryos, the expression of many putative target genes, including cell cy cle-regulated genes, is not affected, CpG islands remain methylation f ree, and active chromatin is formed at the globin loci. However, the e xpression of the methyl-CpG-binding protein MeCP2 is greatly reduced i n Sp1(-/-) embryos. MeCP2 is thought to be required for the maintenanc e of differentiated cells. We suggest that Sp1 is an important regulat or of this process.