Initiation and epigenetic stability of gene silencing in Drosophila

点击翻译按钮获取中文摘要

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.