Functional involvement of RNAs and intrinsically disordered proteins in the assembly of heterochromatin

Abstract

Heterochromatin is a highly condensed chromatin structure observed in the nuclei of eukaryotic cells. It plays a pivotal role in repressing undesired gene expression and establishing functional chromosomal domains, including centromeres and telomeres. Heterochromatin is characterized by specific histone modifications and the formation of higher-order chromatin structures mediated by proteins, such as HP1 and Polycomb repressive complexes (PRCs), which recognize the specific histone modifications. Recent studies have identified the involvement of non-coding RNAs (ncRNAs) and intrinsically disordered proteins (IDPs) in heterochromatin, leading to the proposal of a new model in which liquid-liquid phase separation (LLPS) contributes to heterochromatin formation and function. This emerging model not only broadens our understanding of heterochromatin's molecular mechanisms but also provides insights into its dynamic regulation depending on cellular context. Such advancements pave the way for exploring heterochromatin's role in genome organization and stability, as well as its implications in development and disease.