Comparative analysis of Su(var) chromatin regulators in Drosophila and the mouse

异染色质在保护基因组完整性、维持细胞特性和稳定基因表达程序方面具有重要功能。在过去的15年中，几个表观遗传因素参与异染色质的形成和维持已被描述。特别是，Su（var）突变的PEV（位置效应杂色）在果蝇的屏幕已被证明有助于识别核心异染色质成分，其中大部分是保守的高等真核生物。尽管有这些重大进展，重要的是要注意，只有约25%的约100苏（var）基因座已被分子定义，其余未知的基因座估计编码约70种新型异染色质调节剂。在这里，我们建议使用全基因组测序的方法来快速映射新的苏（var）突变产生的同基因果蝇菌株。这项分析预计将导致约50个新的SU（VAR）因子的识别。果蝇和小鼠的功能分析将集中在选定的保守Su（var）基因，并将解决其在全基因组基因沉默和异染色质形成的分子作用。拟议的研究计划将提供显着的新的见解染色质分区的分子基础和果蝇和哺乳动物异染色质调控的保守方面。

Heterochromatin has important functions in protecting genome integrity, maintaining cell identity and stabilizing gene expression programs. During the last 15 years several epigenetic factors involved in heterochromatin formation and maintenance have been described. In particular, screens for Su(var) mutations of PEV (position effect variegation) in Drosophila have proven instrumental in identifying core heterochromatin components, most of which are conserved in higher eukaryotes. Despite these significant advances, it is important to note that only ~25% of the about 100 Su(var) loci have been molecularly defined, with the remaining unknown loci estimated to encode for approximately 70 novel heterochromatin regulators. Here, we propose to use a genome-wide sequencing approach to rapidly map novel Su(var) mutations that were generated in isogenic Drosophila strains. This analysis is expected to result in the identification of about 50 novel SU(VAR) factors. Functional analysis in Drosophila and mouse will focus on selected conserved Su(var) genes and will address their molecular roles in genome-wide gene silencing and heterochromatin formation. The proposed research plan will provide significant new insights into the molecular basis of chromatin partitioning and conserved aspects of heterochromatin regulation in Drosophila and mammals.