Initiation and epigenetic stability of gene silencing in Drosophila

异染色质诱导的基因沉默是由组蛋白H3-K9甲基转移酶SU（VAR）3-9在发育早期启动的，并在连续的细胞分裂中稳定传递。我们研究的一个中心目标是鉴定控制异染色质基因沉默的表观遗传维持的染色质功能。SU（VAR）3-9的强剂量效应允许研究通过FLIP/FRT依赖性有丝分裂重组的异染色质基因沉默的表观遗传稳定性，用于wm 4 PEV重排中withe基因的非沉默抑制和增强的沉默状态。基于SU（VAR）3-9依赖性基因沉默启动和表观遗传稳定性确立的发育时间的精确测定，将通过转基因分析、基于FLIP/FRT的突变筛选和超过500种可用PEV修饰基因突变的检测，对潜在控制过程进行遗传解剖。在基因检测中，可以鉴定干扰异染色质基因沉默的表观遗传起始或维持的突变。对已鉴定的基因及其产物进行分子分析，可以鉴定参与表观遗传程序启动和维持的未知分子过程，以及鉴定用于重编程的实验工具。

Heterochromatin-induced gene silencing is initiated by the histone H3-K9 methyltransferase SU(VAR)3-9 early in development and stable transmitted over consecutive cell divisions. One central aim of our studies consists in identification of chromatin functions controlling epigenetic maintenance of heterochromatic gene silencing. Strong dosage effects of SU(VAR)3-9 allow to study epigenetic stability of heterochromatic gene silencing by FLIP/FRT dependent mitotic recombination for both the non-silencing suppressed and the enhanced silenced status of the withe gene in the wm4 PEV rearrangement. Based on precise determination of the time in development when SU(VAR)3-9 dependent gene silencing is initiated and its epigenetic stability established, genetic dissection of the underlying control process will be performed by transgene analysis, FLIP/FRT based mutation screens and tests of the over 500 available PEV modifier mutations. In the genetic tests mutations can be identified which interfere with epigenetic initiation or maintenance of heterochromatic gene silencing. Molecular analysis of the identified genes and their products allows identification of the yet unknown molecular processes involved in initiation and maintenance of epigenetic programs as well as to identify experimental tools for reprogramming.