遗传信息编码于基因组DNA序列之中，这些信息的读取则由表观遗传学机制所控制。不同的表观遗传学调控决定了不同组织细胞在形态、功能上的多样性。在物种繁衍过程中，表观遗传机制如何在亲代和子代之间准确传递，是一个有待全面研究的重要科学问题。申报人在先前研究中独立发明的TALE-light技术，实现了对基因组中指定DNA序列的实时活体成像及离体标记。利用该技术，申报人在模式生物果蝇中研究了早期胚胎发育阶段重要表观遗传调控机制—组成型异染色质，在基因组中不同重复序列上的建立过程，揭示了其形成过程的多样性，并发现了一种受母体效应调控、不依赖于H3K9me2/3的异染色质蛋白HP1a招募的新途径。基于这些基础，本项目拟解析转录沉默等组成型异染色质的其他特性在发育过程中的建立步骤，并鉴定各特性建立背后的关键因子，从而全面揭示介导组成型异染色质跨代稳定遗传的“表观遗传记忆"的分子机理。

Genetic information is encoded in the DNA sequences in the genome, and yet the retrieval and interpretation of this information are controlled by epigenetic mechanism, which is the underpinning of the morphological and functional diversity of different cell types seen in one organism. During reproduction, the zygotic genome needs to reset the epigenetic mechanism and remove the constraints in order to regain pluripotency. How is the epigenetic information memorized and subsequently reinstalled during this process is an outstanding question waiting to be fully addressed. We have previously invented a novel sequence-specific DNA visualization method TALE-light, which enables specific labelling of particular genomic locus both live and in fixed tissue samples. Using this method, we studied the emergence of constitutive heterochromatin on different repetitive sequences during Drosophila early embryogenesis, and revealed an unexpected complexity. In particular, we identified a maternally-guided, H3K9me2/3-independent recruiting mechanism of HP1a. Based on these solid preliminary data, in this proposal we want to further interrogate the steps involved in the establishment of different heterochromatic attributes on repetitive sequences, and identify key factors underlying this process. The studies proposed here will uncover how a pivotal epigenetic mechanism—the constitutive heterochromatin—is faithfully transmitted from parents to their offspring during sexual reproduction, and hence provide significant insights into mechanisms of epigenetic inheritance.