Hormone signalling and the control of chromatin differentiation in Drosophila

果蝇的正染色质和异染色质分化始于胚胎发育早期。H3K4去甲基化酶SU(VAR)3-3是人类LSD1的同系物，它通过阻断H3K4me2向异染色质的扩展，并通过与RPD3去乙酰化酶相互作用促进SU(VAR)3-9依赖的H3K9甲基化来定义异染色质-正染色质边界。H3K4me3去甲基化酶LID拮抗RPD3向异染色质的扩展，揭示了一个平行的途径来控制SU(VAR)3-9依赖性H3K9甲基化。这些过程的分析只有在Su（var）显性突变的位置效应杂交种中异色基因沉默的遗传解剖后才成为可能。在胚胎发生过程中启动染色质分化的分子信号尚不清楚。通过TAIMAN和脱皮激素受体共激活蛋白鉴定母体对早期染色质分化的影响，首次对发育过程中控制染色质分化的信号进行分子解剖。TAIMAN依赖信号的功能通过遗传、发育和生化研究确定。结合Chip和Chip分析，我们将研究蜕皮激素信号在控制组蛋白修饰酶和其他参与染色质分化的蛋白质中的作用。

Differentiation of euchromatin and heterochromatin in Drosophila is initiated in early embryogenesis. The H3K4 demethylase SU(VAR)3-3, the homolog of human LSD1, defines heterochromatic- euchromatic boundaries by blocking expansion of H3K4me2 into heterochromatin and by promoting SU(VAR)3-9 dependent H3K9 methylation via interaction with the RPD3 deacetylase. The H3K4me3 demethylase LID antagonizes RPD3 expansion into heterochromatin revealing a parallel pathway in control of SU(VAR)3-9 dependent H3K9 methylation. Analysis of these processes only became feasible after genetic dissection of heterochromatic gene silencing in position-effect variegation with dominant Su(var) mutations. Molecular signals initiating chromatin differentiation in embryogenesis are still unknown. Identification of maternal effects on early chromatin differentiation by TAIMAN an ecdysone receptor coactivator protein allows first time molecular dissection of signals controlling chromatin differentiation in development. Functions involved in TAIMAN dependent signalling are identified by genetic, developmental and biochemical studies. Combined with Chip and ChIP analysis we will study the role of ecdysone signalling in control of histone modifying enzymes and other proteins involved in chromatin differentiation.