Study epigenetic inheritance during development and across generations using multiple model

标题：研究发育过程中和世代之间的表观遗传 模式生物 项目摘要/摘要： 表观遗传学是指通过有丝分裂而遗传的基因表达或功能的影响。 或减数分裂，而不改变初级DNA序列。表观遗传机制发挥着重要作用 在调节细胞身份和活动方面的作用。未能进行适当的表观遗传调控导致 细胞的异常行为，这是许多疾病的基础，如糖尿病、肌肉 营养不良、神经退行性疾病、不孕症和多种癌症。 许多类型的干细胞经历不对称的细胞分裂以产生两个子细胞 有不同的细胞命运：一个是自我更新的干细胞，另一个是分化的子细胞。 我们发现在果蝇雄性生殖系干细胞(GSC)的不对称分裂过程中， 先前存在的组蛋白3(H3)选择性地分离到GSC，而新合成的H3 富含在分化子细胞中。我们的研究提供了第一个直接证据 干细胞在体内细胞不对称分裂期间保留先前存在的组蛋白，这可能 有助于保持他们独特的表观遗传记忆。 这些史无前例的发现使我们处于独特的地位，可以解决长期存在的 关于细胞是否以及如何通过许多细胞维持其表观遗传记忆的问题 这已经成为我们主要的研究重点。我们目前的情况 工作主要有三个方向：(1)了解分子机制和细胞基础 以果蝇雄性GSC为模型系统进行组蛋白不对称遗传的研究 不对称表观遗传在果蝇其他细胞类型中的共性研究 以及在其他生物/系统中，如线虫和小鼠胚胎干细胞； 线虫和线虫代际和跨世代表观遗传的研究 果蝇。我们建议使用分子遗传学、细胞生物学、基因组学和生物物理学 我们研究的方法，这将对广泛的领域产生深远的影响， 包括干细胞生物学、染色质生物学、发育生物学和生殖生物学。

Title: Study epigenetic inheritance during development and across generations using multiple model organisms Project Summary/Abstract: Epigenetics refers to effects on gene expression or function that are inheritable through mitosis or meiosis without altering the primary DNA sequences. Epigenetic mechanisms play important roles in regulating cell identity and activity. Failure in appropriate epigenetic regulation leads to abnormal behaviors of cells, which underlies many diseases such as diabetes, muscular dystrophy, neurodegenerative disease, infertility, and many forms of cancer. Many types of stem cells undergo asymmetric cell divisions to give rise to two daughter cells with distinct cell fates: a self-renewed stem cell and to another daughter cell that differentiates. We found that during the asymmetric division of Drosophila male germline stem cell (GSC), the preexisting histone 3 (H3) are selectively segregated to the GSC whereas newly synthesized H3 are enriched in the differentiating daughter cell. Our studies provide the first direct evidence that stem cells retain preexisting histones during asymmetric cell divisions in vivo, which may contribute to maintain their unique epigenetic memory. These unprecedented discoveries have placed us at a unique position to solve a long-standing question regarding whether and how cells maintain their epigenetic memories through many cell divisions and across generations, which have become our major research focuses. Our current work has three main directions: (1) to understand the molecular mechanisms and cellular basis of asymmetric histone inheritance using Drosophila male GSC as a model system; (2) to investigate the generality of asymmetric epigenetic inheritance in other cell types of Drosophila and in other organisms/systems, such as C.elegans and mouse embryonic stem cells; (3) to study intergenerational and transgenerational epigenetic inheritance in C.elegans and Drosophila. We propose to use molecular genetics, cell biology, genomic, and biophysical approaches in our research, which will have far-reaching impact on a broad range of fields, including stem cell biology, chromatin biology, developmental biology, and reproductive biology.