We do not yet understand how organisms perpetuate even the simplest of gene expression patterns - on in some cells and off in all others. To discover how the regulatory information for such a simple expression pattern is encoded and transmitted as part of the cell code through the single-cell bottleneck between generations, we are using the nematode Caenorhabditis elegans. C. elegans is an ideal animal model for answering this fundamental question because it has a generation time of just 3 days, a fully defined cell lineage, and well-developed tools for experimental manipulation. In this organism, gene regulatory information is partitioned between cells unequally during some cell divisions and equally during other divisions in a stereotyped manner. Understanding how the information for such orchestration of gene expression patterns is transmitted across generations will inform how organisms evolve, what deleterious regulatory changes can be transmitted across generations to cause inherited diseases, and potentially how dysfunction of such developmental control mechanisms could result in the heterogeneity that characterizes gene expression in diseases such as cancer.
Our progress is organized in three sections:
Perpetuation of gene expression patterns. We use phenomena that cause transgenerational gene silencing to discover what promotes and what opposes changes to the cell code. Our analyses have begun to reveal how regulatory molecules gain access to the germline, and how regulatory changes within the germline are transmitted to subsequent generations.
Equal cell division. We use single-cell resolution measurements coupled with lineage analyses to discover mechanisms that determine equal versus unequal gene expression upon cell division. Our analyses have reaveled a developmental mechanism that ensures equal expression from repetitive DNA among sister cells within a tissue.
Methods. We have developed or improved upon methods for the analysis of small RNAs because they are associated with changes in gene expression that persist across generations.
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