MARC Predoctoral Fellowship Program

描述（由申请人提供）：DNA在染色质中的包装极大地影响基因表达。最近的研究结果表明，染色质在细胞核内的定位影响基因的活性。 特别是，核外围似乎包括一个关键的转录控制域。 许多高表达基因定位于核孔。 沉默的染色质也占据特定的核地址。 在酵母和高等真核生物中，沉默的染色质存在于核周边的亚区室中。 在人类中，核纤层蛋白（有助于染色质核区室化的基因）的一些突变导致核纤层蛋白病，包括肌营养不良和哈钦森-吉尔福德早衰综合征。 本提案的目的是了解如何使用酵母作为模型系统确定染色质组织。 Gartenberg实验室最近发现，酵母异染色质通过核膜相关蛋白Esc 1与核周围结合。本研究旨在通过应用分裂泛素酵母双杂交筛选和全基因组细胞学筛选来鉴定Esc 1相互作用的配偶体。 然后，我将使用沉默和DNA定位分析，以了解如何Esc 1有助于核的位置和基因的调控。

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.