LagoZ and LagZ, two genes derived from the LacZ gene to study epigenetics.

The methylation of 5'CpG 3' dinucleotides within genes creates potential ta rgets for protein complexes that bind to methylated DMA sequences and to hi stone deacetylases (MBD-HDAC). This can lead to transcriptional repression by modification of chromatin. To test the importance of this repression in vivo and to determine when during development these epigenetic controls are placed on genes, two novel genes have been engineered by directed mutagene sis of the CpG-rich LacZ gene that are depleted of (LagZ) or completely lac king (LagoZ) CpG sequences. We report that the expression (transcriptional and translational) of the three genes is indistinguishable in transient ass ays in cleaving mouse embryos. Therefore, the complete absence of CpG seque nces within three kilobases of coding sequence is compatible with its maint enance in the nucleus and with its expression. These molecules can now be u sed to study the ontogenesis of the CpG-dependent repressive system in inta ct organisms. (C) 1999 Academie des sciences/Editions scientifiques et medi cales Elsevier SAS.