The Role of Chromatin Modification During Development

描述(由申请人提供)： 染色质修饰是近年来出现的一种新的、重要的基因表达调控机制。然而，染色质修饰剂和由此产生的修饰对建立多细胞生物体中适当的细胞命运和发育的分子网络的影响才刚刚开始出现。为了更好地理解这个问题，本次NRSA将以线虫为体内系统，通过分子、生化和基因组学方法研究HDA-1(组蛋白脱乙酰酶1)在早期胚胎发育中的作用。由于HDA-1对于正确决定细胞命运至关重要，识别直接的HDA-1靶基因以及该蛋白对染色质环境的影响将是理解HDA-1的机制作用的基础。基于这些令人兴奋的发现，关于组蛋白脱乙酰酶在多细胞生物体发育中的体内功能和作用机制的新模型可能会出现。

DESCRIPTION (provided by applicant): Chromatin modification has recently emerged as a novel and important mechanism in the regulation of gene expression. However, the impact that chromatin modifiers and the resulting modifications have on molecular networks establishing proper cell-fate and development in multi-cellular organisms are just beginning to emerge. In order to better understand this question, this NRSA will use the C. elegans as an in vivo system to investigate the role of HDA-1 (histone-deacetylase 1) during early embryogenesis by using molecular, biochemical, and genomic approaches. Since HDA-1 is crucial for proper cell-fate determination, the identification of direct HDA-1 target genes and the impact that this protein has on the chromatin environment will be fundamental in understanding the mechanistic role of HDA-1. Based on these exciting findings, new models are likely to emerge about the in vivo function and mechanism of action of histone deacetylases in the development of a multi-cellular organism.