Shaping Epigenetic Memory via Genomic Bookmarking

TL;DR

This paper introduces a biophysical model where genomic bookmarking stabilizes epigenetic domains, balancing robustness and plasticity, and explains Polycomb mark distribution in Drosophila chromosomes.

Contribution

The study presents a novel biophysical mechanism using genomic bookmarking to maintain epigenetic memory amidst histone modification turnover.

Findings

GBM can explain Polycomb mark distribution in Drosophila.

Genomic bookmarking stabilizes epigenetic patterns.

Model suggests insights into cellular differentiation.

Abstract

Reconciling the stability of epigenetic patterns with the rapid turnover of histone modifications and their adaptability to external stimuli is an outstanding challenge. Here, we propose a new biophysical mechanism that can establish and maintain robust yet plastic epigenetic domains via genomic bookmarking (GBM). We model chromatin as a recolourable polymer whose segments bear non-permanent histone marks (or colours) which can be modified by "writer" proteins. The three-dimensional chromatin organisation is mediated by protein bridges, or "readers", such as Polycomb Repressive Complexes and Transcription Factors. The coupling between readers and writers drives spreading of biochemical marks and sustains the memory of local chromatin states across replication and mitosis. In contrast, GBM-targeted perturbations destabilise the epigenetic patterns. Strikingly, we demonstrate that GBM alone can explain the full distribution of Polycomb marks in a whole Drosophila chromosome. We finally suggest that our model provides a starting point for an understanding of the biophysics of cellular differentiation and reprogramming.