MLL, A MAMMALIAN TRITHORAX-GROUP GENE, FUNCTIONS AS A TRANSCRIPTIONALMAINTENANCE FACTOR IN MORPHOGENESIS

Determinative events in vertebrate embryogenesis appear to require the continuous expression of spatial regulators such as the clustered hom eobox genes. The mechanisms that govern long-term patterns of gene exp ression are not well understood. In Drosophila, active and silent stat es of developmentally regulated loci are maintained by trithorax and P olycomb group, We have examined the developmental role of a mammalian homolog of trx and putative oncogene, Mil, Knockout mice reveal that M ll is required for maintenance of gene expression early in embryogenes is. Downstream targets of MII including Hoxa7 are activated appropriat ely in the absence of Mll but require MII for sustaining their express ion. The Mll-/- phenotype manifests later in development and is charac terized by branchial arch dysplasia and aberrant segmental boundaries of spinal ganglia and somites, Thus, Mll represents an essential mecha nism of transcriptional maintenance in mammalian development, which fu nctions in multiple morphogenetic processes.