Epigenetic Regulation by the aly-class Meiotic Arrest Genes. E.A. Benson, J. Jiang, H. White-Cooper. Department of Zoology, Oxford University, UK.

   In Drosophila spermatogenesis, entry into the meiotic divisions and spermatid differentiation are co-ordinated by the meiotic arrest genes. The aly-class meiotic arrest genes (aly, comr, topi, achi/vis) activate expression of many target genes in Drosophila testes, including cell cycle and morphogenesis genes. aly is homologous to the C. elegans synMuvB pathway gene, lin-9, which negatively regulates vulval induction. SynMuv genes act through the NuRD histone deacetylase and chromatin-remodelling complex to antagonise the RTK-Ras-MAPK inductive signalling cascade. Based on homology to lin-9, we have proposed that epigenetic regulation of gene expression could explain how aly activates so many downstream genes. aly-class meiotic arrest genes may modify chromatin structure at target promoters by promoting histone de-acetylation. Consistent with this hypothesis we have found that bulk histone acetylation is higher in aly-class mutant testes than wild type. Preliminary experiments using chromatin immuno-precipitation suggest that histone acetylation is lower at aly target than non-target promoters.
   Microarray experiments have shown that over 1000 genes are regulated by the aly-class meiotic arrest genes in testes, and there are some differences in target specificity between the DNA binding proteins, Topi and Achi/Vis. Expression patterns of these target genes are being analysed via RT-PCR and RNA in-situ hybridisation in wt and meiotic arrest mutant backgrounds. We have identified two genes, schumacher-levy and hale-bopp, which depend strongly on achi/vis but less on topi, that have a novel expression pattern in testes: weak spotty signal was detected in primary spermatocytes and strong signal resembling a comet was found at the distal end of elongating spermatids. In-situs also indicate that some genes (eg cg2247) require aly-class function for their down-regulation in primary spermatocytes.