Transcription of meiotic cell cycle and terminal differentiation genes depends on a conserved chromatin associated protein, whose nuclear localisation is regulated

The Drosophila always early (aly) gene coordinately regulates meiotic cell cycle progression and terminal differentiation during male gametogenesis. a ly is required for transcription of key G2-M cell cycle control genes and o f spermatid differentiation genes, and for maintenance of normal chromatin structure in primary spermatocytes, We show that aly encodes a homologue of the Caenorhabditis elegans gene lin-9, a negative regulator of vulval deve lopment that acts in the same SynMuvB genetic pathway as the LIN-35 Rb-like protein, The aly gene family is conserved from plants to humans. Aly prote in is both cytoplasmic and nuclear in early primary spermatocytes, then res olves to a chromatin-associated pattern. It remains cytoplasmic in a loss-o f-function missense allele, suggesting that nuclear localisation is critica l for Aly function, and that other factors may alter Aly activity by contro lling its subcellular localisation, MAPK activation occurs normally in aly mutant testes. Therefore aly, and by inference lin-9, act in parallel to, o r downstream of, activation of MAPK by the RTK-Ras signalling pathway. We f avour a model where aly may regulate cell cycle progression and terminal di fferentiation during male gametogenesis by regulating chromatin conformatio n in primary spermatocytes.