Epigenetic switching with asymmetric bridging interactions

Lars Erik J. Skjegstad, Jan Fabio Nickels, Kim Sneppen, Julius B. Kirkegaard*

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

Abstract

Gene expression states are often stably sustained in cis despite massively disruptive events like DNA replication. This is achieved by on-going enzymatic activity that maintains parts of the DNA in either heterochromatic (packed) or euchromatic (free) states, each of which is stabilized by both positive feedback and bridging interactions between individual nucleosomes. In contrast to condensed matter, however, the dynamics is not only governed by equilibrium binding interactions but is also mediated by enzymes that recognize and act on specific amino acid tails of the nucleosomes. The mechanical result is that some nucleosomes can bind to one another and form tightly packed polymer configurations, whereas others remain unbound and form free, noncompact polymer configurations. Here, we study the consequences of such an asymmetric interaction pattern on the dynamics of epigenetic switching. We develop a 3D polymer model and show that traits associated with epigenetic switching, such as bistability and epigenetic memory, are permitted by such a model. We find, however, that the experimentally observed burst-like nature of some epigenetic switches is difficult to reproduce by this biologically motivated interaction. Instead, the behavior seen in experiments can be explained by introducing partial confinement, which particularly affects the euchromatic regions of the chromosome.

Original languageEnglish
JournalBiophysical Journal
Volume122
Issue number12
Pages (from-to)2421-2429
Number of pages9
ISSN0006-3495
DOIs
Publication statusPublished - 20 Jun 2023

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© 2023 Biophysical Society

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