Transcriptional control requires the spatially and temporally coordinated action of many macromolecular complexes. Chromosomal proteins, transcription factors, co-activators and components of the general transcription machinery, including RNA polymerases, often use structurally or stoichiometrically ill-defined regions for interactions that convey regulatory information in processes ranging from chromatin remodeling to mRNA processing. Determining the functional significance of intrinsically disordered protein regions and developing conceptual models of their action will help to illuminate their key role in transcription regulation. Complexes comprising disordered regions often display short recognition elements embedded in flexible and sequentially variable environments that can lead to structural and functional malleability. This provides versatility to recognize multiple targets having different structures, facilitate conformational rearrangements and physically communicate with many partners in response to environmental changes. All these features expand the capacities of ordered complexes and give rise to efficient regulatory mechanisms.At the critical intersection between signaling pathways and the process of gene expression, transcription regulation controls and influences many cellular and physiological processes, from cell differentiation and development to metabolic responses to environmental stimuli. Transcription regulation depends on communication and interaction between many large multiprotein complexes, which results in transmission of regulatory information to the RNA polymerases that carry out the synthesis of mRNA from a chromosomal DNA template. In eukaryotic organisms, diverse arrays of proteins are involved in every aspect of transcription regulation, from chromatin remodeling to mRNA processing. These include (i) the histones, chromatin and macromolecular complexes that modify chromatin structure and provide access to the DNA, (ii) transcription factors that bind to upstream regulatory sequences, (iii) co-activators that communicate signals to the core transcription machinery and (iv) general Early observations about two decades ago indicated that various components of the transcription machinery, such as the transactivator domains (TADs) of the GCN4 and GAL4 transcription factors and the C-terminal domain (CTD) of RNA polymerase II (RNAP II), cannot be characterized by a well-defined three-dimensional structure, and that their functions may even be independent of their actual sequences1. These domains were envisaged to act as charged 'blobs' or 'noodles' that would allow recognition of interacting partners of variable architectures and form nontraditional assemblages. Although this scenario has been refined subsequently2, it has been recognized only recently that structurally ill-defined proteins and protein segments, termed intrinsically disordered proteins (IDPs) and intrinsically disordered regions (IDRs), are abundant in eukaryotic proteomes. For example, >50% of proteins are p...