TY - JOUR

T1 - Epigenetic switching with asymmetric bridging interactions

AU - Skjegstad, Lars Erik J.

AU - Nickels, Jan Fabio

AU - Sneppen, Kim

AU - Kirkegaard, Julius B.

N1 - Publisher Copyright: © 2023 Biophysical Society

PY - 2023/6/20

Y1 - 2023/6/20

N2 - 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.

AB - 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.

U2 - 10.1016/j.bpj.2023.04.019

DO - 10.1016/j.bpj.2023.04.019

M3 - Journal article

C2 - 37085994

AN - SCOPUS:85158043671

VL - 122

SP - 2421

EP - 2429

JO - Biophysical Society. Annual Meeting. Abstracts

JF - Biophysical Society. Annual Meeting. Abstracts

SN - 0523-6800

IS - 12

ER -