组蛋白编码（Histone Code）是表观遗传控制的分子基础之一，在发育过程中其形成具有组织和基因特异性的特点。然而，其分子机制并不十分清楚。我们前期研究发现PTIP对在特定发育过程的组蛋白编码形成中起重要作用，细胞中的Microarray分析表明，PTIP可能直接参与了百余Polycomb基因家族靶基因的调控（Fang et al., 2009）。本研究将以果蝇为模式动物，通过胚胎中PTIP与DNA相互作用的全基因组分析，并进一步用果蝇遗传学的方法深入研究PTIP在组蛋白修饰中的在体作用机制。另一方面，鉴于PTIP在DNA损伤修复中的必要作用，我们将观察辐射后胚胎中PTIP与DNA结合的动态变化，以阐明PTIP参与转录调控与DNA损伤修复这两个生物学过程的相互联系和功能区分。我们希望以此为例阐明组蛋白编码通过像PTIP这样的蛋白因子（我们称为向导蛋白）来实现精密调控。

Epigenetic control relies in part on Histone modifications, also termed as Histone code, which is apparently regulated in tissue and gene specific manners. However, the underlying mechanisms remain poorly understood. We and others have previously shown that PTIP is among essential elements for the proper Histone code formation. In addition, we have shown that PTIP mediates specifically the anterior/posterior patterning processes in flies. We have also demonstrated that PTIP may be involved in the regulation of up to a hundred of genes in Drosophila cells by means of microarray analysis (Fang et al., 2009). In this grant application, we propose to carry out genome-wide profiling of PTIP, as well as its known associated proteins, such as UTX, in staged fly embryos. Upon gain of information on the dynamics of PTIP in embryo development, we will make use of fly genetics to further study in detail one or two direct target genes of PTIP. On the other hand, since PTIP also associates with DNA damage response pathway, we plan to sample PTIP binding data by ChIP analysis in irradiated embryos. In combination with Histone modification analysis, we aim to understand how PTIP may discriminate in mediating different biological processes, such as transcription regulation and DNA damage response. Our hope is to present an example that Histone code dynamics is tightly regulated by epigenetic guider proteins, such as PTIP.