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Organization and regulation of gene transcription

Abstract

The regulated transcription of genes determines cell identity and function. Recent structural studies have elucidated mechanisms that govern the regulation of transcription by RNA polymerases during the initiation and elongation phases. Microscopy studies have revealed that transcription involves the condensation of factors in the cell nucleus. A model is emerging for the transcription of protein-coding genes in which distinct transient condensates form at gene promoters and in gene bodies to concentrate the factors required for transcription initiation and elongation, respectively. The transcribing enzyme RNA polymerase II may shuttle between these condensates in a phosphorylation-dependent manner. Molecular principles are being defined that rationalize transcriptional organization and regulation, and that will guide future investigations.

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Fig. 1: Key steps of gene transcription.
Fig. 2: Structures of eukaryotic transcription PICs.
Fig. 3: Pol II progression through the transcription cycle.
Fig. 4: Switch from Pol II pausing to active elongation.
Fig. 5: Condensate-based model of Pol II transcription.

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Acknowledgements

I would like to thank past and present members of the laboratory. I apologize to those colleagues whose work could not be cited owing to space restraints. I am supported by the Deutsche Forschungsgemeinschaft (SFB860, SPP1935 and EXC 2067/1- 390729940), the European Research Council (Advanced Investigator Grant TRANSREGULON, grant agreement No 693023), and the Volkswagen Foundation.

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Cramer, P. Organization and regulation of gene transcription. Nature 573, 45–54 (2019). https://doi.org/10.1038/s41586-019-1517-4

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