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Malleable machines take shape in eukaryotic transcriptional regulation

Nature Chemical Biology volume 4, pages 728–737 (2008)Cite this article

Abstract

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.

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Figure 1: Schematic representation of the four main (highly interdependent) components of the eukaryotic transcription machinery.
Figure 2: Molecular recognition by intrinsically disordered proteins.
Figure 3: Domain structure of CBP/p300 transcriptional co-activator and three-dimensional structures of complexes of globular CBP domains with disordered transcription factors bound.

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Acknowledgements

M.F. is supported by MRTN-CT-2005-019566 of the European FP6 and by the Bolyai János fellowship; P.T. is supported by Országos Tudományos Kutatási Alapprogramok NK 71582, ETT 245/2006; and I.S. is supported by Országos Tudományos Kutatási Alapprogramok K72569. V.N.U. is supported by the grants R01 LM007688-01A1 (to A.K. Dunker and V.N.U.) and GM071714-01A2 (to A.K. Dunker and V.N.U.) from the US National Institutes of Health. We gratefully acknowledge the support of the Indiana University, Purdue University at Indianapolis Signature Centers Initiative. J.C.H. is supported by US National Institutes of Health grants GM45916 and GM66834. F.J.A. is supported by funds from the US National Institute of General Medical Sciences and the Leukemia and Lymphoma Society of America. The authors are grateful to C. Oldfield for his contribution to Figure 2.

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Authors and Affiliations

  1. Institute of Enzymology, Biological Research Center, Hungarian Academy of Sciences, Karolina ut 29, H-1113, H-1518 Budapest, Hungary.,

    Monika Fuxreiter, Peter Tompa & István Simon

  2. Department of Biochemistry and Molecular Biology, Institute for Intrinsically Disordered Protein Research, Center for Computational Biology and Bioinformatics, Indiana University School of Medicine, Indianapolis, Indiana 46202-2111, USA.,

    Vladimir N Uversky

  3. Department of Biochemistry and Molecular Biology, Colorado State University, Fort Collins, Colorado 80523-1870, USA.,

    Jeffrey C Hansen

  4. Department of Cell Biology, The Scripps Research Institute, La Jolla, California 92037, USA.,

    Francisco J Asturias

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Fuxreiter, M., Tompa, P., Simon, I. et al. Malleable machines take shape in eukaryotic transcriptional regulation. Nat Chem Biol 4, 728–737 (2008). https://doi.org/10.1038/nchembio.127

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