Dissertation Research: FUNCTIONAL CONSEQUENCES OF ADAPTIVE VARIATION AT CHROMATIN REMODELING GENES

染色质的动态性质(即DNA与其蛋白质包装复合)与整个基因组的动态基因表达有关。染色质的动态是环境敏感的，然而染色质重构体(调节这些动态的蛋白质)对适应新的环境条件的贡献尚不清楚。初步工作描述了几个染色质重塑基因，它们在通常研究的果蝇黑腹果蝇中具有局部适应的特征。这个项目将通过测量基因表达的模式来表征替代染色质重塑基因变体的作用，并描述染色质状态(静态或动态)对环境变化的自然变化。这些问题将通过能够在整个基因组内研究基因表达和蛋白质-DNA相互作用的技术来解决。这项研究将揭示染色质重塑蛋白的新角色。它还将描述可能揭示新基因功能的新基因变体。最近的研究表明，染色质重塑的突变与包括癌症在内的许多人类疾病相关的基因表达谱异常之间存在联系。在果蝇中记录的与环境变化相关的自然变异，特别是环境压力，可能有助于揭示与染色质生物学相关的人类疾病变异。

The dynamic nature of chromatin (i.e., DNA complexed with its protein packaging) is associated with dynamic gene expression across the genome. Chromatin dynamics are environment-sensitive, yet the contribution of chromatin remodelers (proteins that modulate these dynamics) to adaptation to novel environmental conditions is unknown. Preliminary work described several chromatin remodeling genes that bear the signature of local adaptation in the commonly studied fruit fly Drosophila melanogaster. This project will characterize the roles of the alternative chromatin remodeling gene variants by measuring patterns of gene expression, and to describe natural variation in chromatin state (static or dynamic) in response to environmental variation. These questions will be addressed using technology that enables gene expression and protein-DNA interactions to be studied within entire genomes.This research will shed light on a novel role for chromatin remodeling proteins. It will also describe novel gene variants that may reveal novel gene function. Recent studies demonstrate a link between mutations in chromatin remodeling and aberrant gene expression profiles associated with many human diseases, including cancer. Natural variation associated with environmental variation, specifically environmental stress, documented in Drosophila may shed light on human disease variation associated with chromatin biology.