Overview

What is epigenetic inheritance?

Epigenetic inheritance refers to the ability of the same genome to produce multiple distinct, yet stable, phenotypes, such as the various differentiated cell types in multicellular organisms. A straightforward example is that of inheritance of cell state, as the many distinct cell types in a multicellular organism are stably maintained – liver cells divide into two liver cells and not into a fibroblast and a neuron – despite these cell types all sharing essentially identical genomes. Decades of study have identified a variety of molecular mechanisms that are required for transmission of epigenetic information from one generation to the next. Our lab focuses on two broad areas of epigenetic regulation, described below.

Chromatin structure and function

Chromatin structure – the packaging of the genome into a repeating subunit known as the nucleosome – is a key player in cellular differentiation and cell state maintenance, and many genes identified in early genetic studies on D. melanogaster homeotic transformations were later revealed to be chromatin regulators. Chromatin architecture can affect gene regulation in many ways – access of most DNA-binding regulatory proteins to their target sites is broadly inhibited at nucleosome-occluded DNA sites, while the chemical state of the nucleosome can influence the targeting or activity of many other regulatory proteins – meaning that the chromatin landscape can act essentially as a “filter” that influences the readout of genomic information. Our lab studies the structure and function of the budding yeast genome, seeking to understand the rules underlying the folding of the genome, and the mechanistic basis for copying and/or re-establishing the genomic folding state every cell cycle.

Paternal effects in mammals

Not only is epigenetic information involved in cell fate determination and stability, but it is increasingly appreciated that epigenetic information in the germline can impact the phenotype of future generations. One implication of this is that it provides a potential basis by which the environment experienced in one generation could influence the phenotype in future generations. This idea, essentially a resurrection of the historical concept of “the inheritance of acquired characters”, has motivated us for over a decade to study whether paternal environmental conditions have any influence over the phenotype of offspring. We have established paternal effect model systems based on various dietary challenges, as well as nicotine exposure, and are actively investigating the mechanistic basis by which a father’s experiences affect his children. See here [RO1] for a lay summary of these ideas.