Dissecting the Regulation of Gene Expression during C. elegans Embryogenesis

动物的发育需要单个细胞的后代（受精卵）分化成所有的细胞。 生物体的T ^ES。细胞区别于其他细胞的一种方式是通过差异化的 1 转录调节蛋白的表达。每个细胞中转录因子表达的特定模式 可以反过来调节下游的分化决策。这个项目的重点是定义如何转录 在发育过程中，这些因素使细胞类型的排列越来越复杂。最终 这项工作的目标是揭示转录因子之间相互作用的一般规则， 染色质修饰和其它基因组特征导致下游靶基因的适当调节。 我们的目标是在C. elegans 通过结合遗传扰动和体内分辨率表达谱分析，同时，我们将测试 细胞命运的转录因子调控的组合模型，并确定直接的功能靶点， 通过检查每个因子的异位表达的后果来确定发育活性转录因子。 当与目前可用的其他类型的基因组数据相结合时，这些实验的结果将 提供了基础，以确定一般规则的转录因子结合位点的活动。

Animal development requires the differentiation of the progeny ofa single cell, the zygote, into all of the cell tj^es of the organism. One way that cells distinguish themselves from other cells is through differential 1 expression of transcriptional regulatory proteins. Specific patterns of transcription factor expression in each cell can in turn regulate downstream differentiation decisions. This project focuses on defining how transcription factors pattern the increasingly complex array of cell types during the progression of development. The ultimate goal of this work is to uncover general rules through which interactions between transcription factors, chromatin modifications and other genomic features lead to appropriate regulation of downstream target genes. We aim to generate a validated cellular resolution regulatory network of early development in the C. elegans embryo by combining genetic perturbation with in vivo resolution expression profiling. In parallel, we will test combinatorial models of transcription factor regulation of cell fate and identify direct functional targets for developmentally active transcription factors by examining the consequences of ectopic expression of each factor. When combined with other types of genomic data currently available, the results ofthese experiments will provide the basis to identify general rules governing the activity of transcription factor binding sites.