Dissecting the Regulation of Gene Expression during C. elegans Embryogenesis

动物的发育需要将单个细胞的后代，即受精卵，分化成所有的细胞。 生物体的TJ‘s。细胞区别于其他细胞的一种方式是通过分化 1 转录调控蛋白的表达。转录因子在每个细胞中的特定表达模式 可以反过来调节下游的差异化决策。这个项目的重点是定义转录如何 在发育过程中，各种因素形成了日益复杂的细胞类型阵列。终极的 这项工作的目标是揭示转录因子之间相互作用的一般规律， 染色质修饰和其他基因组特征导致对下游靶基因的适当调节。 我们的目标是在线虫的早期发育中产生一个经过验证的细胞分辨率调节网络 通过将遗传扰动与体内分辨率表达谱相结合来获得胚胎。同时，我们将测试 转录因子调控细胞命运的组合模型和确定直接的功能靶点 通过检测每个因子异位表达的后果来激活发育活性的转录因子。 当结合目前可用的其他类型的基因组数据时，这些实验的结果将 为确定控制转录因子结合位点活性的一般规则提供基础。

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.