MARC Predoctoral Fellowship Program

描述(申请人提供)：染色质中DNA的包装对基因表达有很大影响。最近的发现表明，染色质在细胞核内的位置会影响基因的活性。特别是，核外周似乎包含一个对转录控制至关重要的区域。许多高表达的基因定位于核孔。沉默的染色质也占据着特定的核地址。在酵母和高等真核生物中，沉默的染色质存在于核外围的亚室中。在人类中，层粘连蛋白的一些突变会导致染色质的核分区，导致椎板病变，包括肌肉营养不良和Hutchinson-Gilford Progeria综合征。这项建议的目标是了解如何使用酵母酵母作为模型系统来确定染色质组织。Gartenberg实验室最近发现，酵母异染色质通过核膜相关蛋白Esc1结合到细胞核外围。我的目标是通过采用分裂的泛素酵母双杂交筛选和全基因组细胞学筛选来鉴定ESc1相互作用伙伴。然后，我将使用沉默和DNA定位分析来了解ESc1如何对基因的核位置和调控做出贡献。

DESCRIPTION (provided by applicant): The packaging of DNA in chromatin greatly influences gene expression. Recent findings indicate that chromatin positioning within the nucleus influences gene activity. In particular, the nuclear periphery appears to comprise a domain critical for transcriptional control. Many highly expressed genes localize to nuclear pores. Silenced chromatin also occupies a specific nuclear address. In yeast and in higher eukaryotes, silenced chromatin resides in sub-compartments at the nuclear periphery. In humans, some mutation of lamins, genes that contribute to the nuclear compartmentalization of chromatin, lead to laminopathies, including muscular dystrophy and Hutchinson-Gilford Progeria Syndrome. The goal of this proposal is to understand how chromatin organization is determined using yeast Saccharomyces as a model system. The Gartenberg lab recently showed that yeast heterochromatin is bound to the nuclear periphery by a nuclear membrane-associated protein Esc1.I aim to identify Esc1 interacting partners by adapting the split ubiquitin yeast two hybrid screen and by using and a whole genome cytological screen. I will then use silencing and DNA localization assays to learn how Esc1 contributes to the nuclear position and regulation of genes.