From chromosomal protein disorder to chromatin phase separation

In recent years, two seemingly unrelated topics, protein disorder and phase separation, have become highly significant in biology. In this way, intrinsically disordered proteins and liquid-liquid phase separation have become two of the hottest topics in the field. In this review, we provide a brief description of intrinsic protein disorder and its effects on the main protein constituents of chromatin, from histones to high-mobility group proteins, heterochromatin HP1, the neuronal methyl-CpG binding protein 2, and the highly specialized arginine-rich protamines of sperm. Following this, we provide a general overview of the role of their intrinsically disordered regions (IDRs) in chromatin condensate formation and present the evolving understanding of the amino acid sequence grammar of IDRs that determines their involvement in in the formation of chromatin condensates. After a brief overview of the theoretical aspects beyond this process, we describe how it is connected to the folding of somatic and male germ cell chromatin. Somatic cell chromatin is organized into compartments. We discuss the characteristics of the phase-separated transcription condensate in compartment A (euchromatin), including the specialized biomolecular condensate in which replication-dependent histone genes are transcribed, and the differential structure and role of HP1 alpha in compartment B heterochromatin compaction across different species.