Hormone signalling and the control of chromatin differentiation in Drosophila

果蝇常染色质和异染色质的分化起始于胚胎发育早期。H3 K4脱甲基酶SU（VAR）3-3是人LSD 1的同源物，通过阻断H3 K4 me 2扩增到异染色质中并通过与RPD 3脱乙酰酶相互作用促进SU（VAR）3-9依赖性H3 K9甲基化来限定异染色质-常染色质边界。H3 K4 me 3去甲基化酶LID拮抗RPD 3向异染色质中的扩增，揭示了控制SU（VAR）3-9依赖性H3 K9甲基化的平行途径。这些过程的分析，只有成为可行后，异染色质基因沉默的位置效应杂色与显性苏（var）突变的遗传解剖。在胚胎发生中启动染色质分化的分子信号仍然是未知的。通过蜕皮激素受体辅激活蛋白TAIMAN鉴定母体对早期染色质分化的影响，首次从分子水平上剖析了发育中控制染色质分化的信号。TAIMAN依赖性信号传导中涉及的功能通过遗传、发育和生物化学研究来鉴定。结合芯片和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.