MARC Predoctoral Fellowship Program

描述（申请人提供）：DNA在染色质中的包装对基因表达有很大影响。最近的研究结果表明，细胞核内染色质的定位影响基因的活性。特别是，核外围似乎包含一个对转录控制至关重要的结构域。许多高表达基因定位于核孔。沉默的染色质也占据一个特定的核地址。在酵母和高等真核生物中，沉默的染色质存在于核周围的亚室中。在人类中，一些导致核染色质区室化基因的层粘连蛋白突变导致层粘连病，包括肌肉萎缩症和哈钦森-吉尔福德早衰综合征。本提案的目标是了解如何染色质组织是确定使用酵母酵母作为模型系统。Gartenberg实验室最近发现酵母异染色质通过核膜相关蛋白Esc1与核外周结合。我的目标是通过适应分裂泛素酵母双杂交筛选和使用全基因组细胞学筛选来确定Esc1相互作用的伙伴。然后，我将使用沉默和DNA定位分析来了解Esc1如何影响基因的核位置和调控。

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.