Chemical and biophysical methods to explore dynamic mechanisms of chromatin silencing

Chromatin, the nucleoprotein complex organizing the genome, is central in regulating gene expression and genome organization. Chromatin conformational dynamics, controlled by histone post-translational modifications (PTM) and effector proteins, play a key role in this regulatory function. Recent developments in chemical biology, cell biology, and biophysics sparked important new studies, which probe direct causal connections between histone PTMs, chromatin effector proteins that write or read these modifications, and the involved functional chromatin states. In particular, the mechanisms of heterochromatin silencing have been explored in great detail in recent years. These studies revealed the highly dynamic nature of this chromatin state, its conformational heterogeneity, and different mechanisms of its formation. Here, we review how chemical biology and biophysics shaped our current understanding of the dynamic processes observed in heterochromatin and discuss the emerging technologies to detect chromatin organization directly in the cellular environment.