How is the expression pattern of a gene perpetuated?

Life has diversified since its origin through bottleneck stages that separate successive generations. Each organism develops from the bottleneck stage, typically a single cell, with two distinct stores of information. One is the linear DNA sequence that is replicated during cell divisions. The other is the three-dimensional arrangement of molecules that dictates what is made using the DNA sequence and changes during development but returns to a similar configuration at the start of each generation. These two interdependent stores of information – one replicating with every cell division (grey) and the other cycling with a period of one generation (colors) – coevolve and together form the cell code for making an organism (see video). This perspective impacts our understanding of the origins of inherited diseases, the course of evolution, and the synthesis of new life.

To understand how the cell code of an organism is set up and transmitted from one generation to the next, we need to ask questions about how processes are perpetuated. Our lab is using the simple worm C. elegans to understand how the expression pattern of a gene is perpetuated. Taking advantage of our recent ability to induce transgenerational epigenetic inheritance, i.e. modify non-genetic aspects of the cell code, our goal is to use reductionist, systems, and engineering approaches to address this question. These studies will begin to reveal the logic of how the information required to build and perpetuate an animal is transmitted across generations.

To build an organism from its cell code in every generation, gene expression patterns need to be orchestrated throughout development. Organisms need to control the equal versus unequal partitioning of gene regulatory information upon cell division, the switch between both forms of cell division, and the coordination of gene expression between cells. While mechanisms of unequal or asymmetric cell division have been studied in the context of development, much less is known about symmetric or equal cell divisions and how organisms switch from asymmetric to symmetric divisions. Yet, the entire cell code is capable of being divided equally as revealed by the existence of twins and by experimental manipulation. Therefore, we are interested in understanding the mechanisms that enable equal cell division, the switch between equal and unequal cell divisions, and the coordination of gene expression between cells. These studies will reveal the regulatory mechanisms that orchestrate gene expression in an organism.