Disordered regions tune order in chromatin organization and function

Intrinsically disordered proteins or hybrid proteins with ordered domains and disordered regions (both collectively designated as IDP(R)s) defy the well-established structure-function paradigm due to their ability to perform multiple biological functions even in the absence of a well-defined 3D structure. IDP(R)s have a unique ability to exist as a functional heterogeneous ensemble, where they adopt multiple thermodynamically stable conformations with low energy barriers between states. The resultant structural plasticity or conformational adaptability provides them with a high functional diversity and ease of regulation. Hence, IDP(R)s are highly efficient biological machinery to mediate intricate cellular functions such as signaling, gene expression, and assembly of complex structures. One such structure is the nucleoprotein complex known as Chromatin. Interestingly, the proteins involved in shaping up the structure and function of chromatin are abundant in disordered regions, which serve more than just as mere flexible linkers. The disordered regions are involved in crucial processes such as gene expression regulation, chromatin architecture maintenance, and liquid-liquid phase separation initiation. This review is an attempt to explore the advantages and the functional and regulatory roles of intrinsic disorder in several Chromatin Associated Proteins from a mechanistic standpoint.