Nuclear envelope and chromatin choreography direct cellular differentiation

The nuclear envelope plays an indispensable role in the spatiotemporal organization of chromatin and transcriptional regulation during the intricate process of cell differentiation. This review outlines the distinct regulatory networks between nuclear envelope proteins, transcription factors and epigenetic modifications in controlling the expression of cell lineage-specific genes during differentiation. Nuclear lamina with its associated nuclear envelope proteins organize heterochromatin via Lamina-Associated Domains (LADs), proximal to the nuclear periphery. Since nuclear lamina is mechanosensitive, we critically examine the impact of extracellular forces on differentiation outcomes. The nuclear envelope is spanned by nuclear pore complexes which, in addition to their central role in transport, are associated with chromatin organization. Furthermore, mutations in the nuclear envelope proteins disrupt differentiation, resulting in developmental disorders. Investigating the underlying nuclear envelope controlled regulatory mechanisms of chromatin remodelling during lineage commitment will accelerate our fundamental understanding of developmental biology and regenerative medicine.