A novel member of murine Polycomb-group proteins, Sex comb on midleg homolog protein, is highly conserved, and interacts with RAE28/mph1 in vitro

The Polycomb group of (PcG) genes were originally described in Drosophila, but many PcG genes have mammalian homologs. Genetic studies in flies and mi ce show that mutations in PcG genes cause posterior transformations caused by failure to maintain repression of homeotic loci, suggesting that PcG pro teins have conserved functions. The Drosophila gene Sex comb on midleg (Scm ) encodes an unusual PcG protein that shares motifs with the PcG protein po lyhomeotic, and with a Drosophila tumor suppressor, lethal(3)malignant brai n tumor (1(3)mbt), Expressed sequence tag (EST) databases were searched to recover putative mammalian Scm homologs, which were used to screen murine c DNA libraries. The recovered cDNA encodes two mbt repeats and the SPM domai n that characterize Scm, but lacks the cysteine clusters and the serine/thr eonine-rich region found at the amino terminus of Scm. Accordingly, we have named the gene Sex comb on midleg homolog 1 (Scmh1). Like their Drosophila counterparts, Scmh1 and the mammalian polyhomeotic homolog RAE28/mph1 inte ract in vitro via their SPM domains. We analyzed the expression of Scmh1 an d rae28/mph1 using northern analysis of embryos and adult tissues, and in s itu hybridization to embryos. The expression of Scmh1 and me28/mph1 is well correlated in most tissues of embryos. However, in adults, Scmh1 expressio n was detected in most tissues, whereas mph1/rae28 expression was restricte d to the gonads. Scmh1 is strongly induced by retinoic acid in F9 and P19 e mbryonal carcinoma cells. Scmh1 maps to 4D1-D2.1 in mice. These data sugges t that Scmh1 will have an important role in regulation of homeotic genes in embryogenesis and that the interaction with RAE28/mph1 is important in viv o.