The Role of Chromatin Modification During Development

描述（由申请人提供）： 染色质修饰是近年来发现的一种新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在多细胞生物体中建立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，NRSA将使用C。elegans作为一个体内系统，研究HDA-1（组蛋白脱乙酰酶1）在早期胚胎发生过程中的作用，通过使用分子，生物化学和基因组学方法。由于HDA-1对于正确的细胞命运决定至关重要，因此直接HDA-1靶基因的鉴定以及该蛋白对染色质环境的影响将是理解HDA-1机制作用的基础。基于这些令人兴奋的发现，新的模型可能会出现关于在体内的功能和作用机制的组蛋白去乙酰化酶在多细胞生物体的发展。

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.