Top-down and bottom-up models of the DNA methylation landscape

11 February 2022

Elizabeth Read
Department of Chemical and Biological Engineering
UC Irvine

zoom recording

Abstract

In dividing cells, the epigenetic landscape is dismantled and then reestablished with every cycle of DNA replication. Heritability of the epigenetic code over cycles of replication is essential for the reliable maintenance of cell identity. Yet, the molecular mechanisms underlying this heritability are not fully understood.

In the Read lab, we are interested in bridging "top-down" with "bottom-up" modeling to maximize knowledge gained from data. Here, the former refers to modeling driven by experimental data, with minimal assumptions, while the latter refers to modeling driven by mechanistic hypotheses, making use of simulations to study their implications. I will present an example of how we can bridge these two distinct approaches. We found that stochastic modeling of enzymatic processes responsible for maintaining the DNA methylation landscape aids interpretation of local correlations derived from epigenome sequencing. Our findings shed light on how—and to what extent—genomic sites act independently versus collectively during maintenance methylation, with implications for stability of the epigenetic landscape.

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