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RNA polymerase II transcription compartments: from multivalent chromatin binding to liquid droplet formation?

Nature Reviews Molecular Cell Biology volume 22, pages 645–646 (2021)Cite this article

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Recent studies invoke phase separation as a mechanism underlying the formation of ‘transcriptional condensates’. However, similarities between transcriptional condensates and the previously introduced ‘transcription factories’ model raise the question of what distinguishes the two models. One crucial aspect to consider is the contribution of intrinsically disordered regions in transcription-relevant factors.

In cell nuclei, concentration gradients equilibrate within seconds owing to fast diffusion of macromolecules. Thus, one would expect proteins and RNA involved in transcription to become homogeneously distributed as soon as they are released from chromatin. However, transcription by RNA polymerase II (Pol II) was shown already in the early 1990s to preferentially occur in distinct 50–180 nm nuclear foci of active Pol II holoenzymes named ‘transcription factories’1. Approximately 1,000–2,500 such factories can be detected per nucleus, depending on cell type. Active Pol II in its preinitiation state at these loci displays residence times of ~10 seconds, whereas elongating Pol II is stably bound to the DNA until a transcript is synthesized1,2. The mechanisms guiding the assembly of Pol II transcription compartments, however, remained enigmatic. A recent suggestion is that RNA polymerases, promoter and enhancer sequences and associated factors undergo phase separation through multivalent interactions, to create an exclusionary local protein–RNA environment with characteristic physicochemical properties3,4,5,6. A frequently used, yet simplistic analogy for this process is the demixing of oil in water.

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Acknowledgements

The work of K.R. on phase separation is funded by the Deutsche Forschungsgemeinschaft (DFG) in Priority Program 2191 ‘Molecular Mechanisms of Functional Phase Separation’ via grant RI1283/16-1. A.P. is also supported by the DFG via the Priority Program 2202 ‘Spatial Genome Architecture in Development and Disease’ (Project 422389065) and the TRR81 Collaborative Research Center (Project 109546710).

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  1. Division of Chromatin Networks, German Cancer Research Center (DKFZ) and Bioquant, Heidelberg, Germany

    Karsten Rippe

  2. Translational Epigenetics Group, Institute of Pathology, University Medical Center Göttingen, Göttingen, Germany

    Argyris Papantonis

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  1. Karsten Rippe
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Correspondence to Karsten Rippe or Argyris Papantonis.

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Rippe, K., Papantonis, A. RNA polymerase II transcription compartments: from multivalent chromatin binding to liquid droplet formation?. Nat Rev Mol Cell Biol 22, 645–646 (2021). https://doi.org/10.1038/s41580-021-00401-6

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