FACT maintains chromatin architecture and thereby stimulates RNA polymerase II 
pausing during transcription in vivo

Žumer, Kristina; Ochmann, Moritz; Aljahani, Abrar; Zheenbekova, Aiturgan; Devadas, Arjun; Maier, Kerstin C.; Rus, Petra; Neef, Ute; Oudelaar, Aukje Marieke; Cramer, Patrick

doi:10.1016/j.molcel.2024.05.003

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FACT maintains chromatin architecture and thereby stimulates RNA polymerase II pausing during transcription in vivo

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Žumer, Kristina
Department of Molecular Biology, Max Planck Institute for Multidisciplinary Sciences, Max Planck Society;

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Ochmann, Moritz
Department of Molecular Biology, Max Planck Institute for Multidisciplinary Sciences, Max Planck Society;

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Aljahani, Abrar
Lise Meitner Group Genome Organization and Regulation, Max Planck Institute for Multidisciplinary Sciences, Max Planck Society;

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Zheenbekova, Aiturgan
Department of Molecular Biology, Max Planck Institute for Multidisciplinary Sciences, Max Planck Society;

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Devadas, Arjun
Department of Molecular Biology, Max Planck Institute for Multidisciplinary Sciences, Max Planck Society;

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Maier, Kerstin C.
Department of Molecular Biology, Max Planck Institute for Multidisciplinary Sciences, Max Planck Society;

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Rus, Petra
Department of Molecular Biology, Max Planck Institute for Multidisciplinary Sciences, Max Planck Society;

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Oudelaar, Aukje Marieke
Lise Meitner Group Genome Organization and Regulation, Max Planck Institute for Multidisciplinary Sciences, Max Planck Society;

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Cramer, Patrick
Department of Molecular Biology, Max Planck Institute for Multidisciplinary Sciences, Max Planck Society;

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Citation

Žumer, K., Ochmann, M., Aljahani, A., Zheenbekova, A., Devadas, A., Maier, K. C., et al. (2024). FACT maintains chromatin architecture and thereby stimulates RNA polymerase II pausing during transcription in vivo. Molecular Cell, 84(11), 2053-2069.e9. doi:10.1016/j.molcel.2024.05.003.

Cite as: https://hdl.handle.net/21.11116/0000-000F-5BF8-4

Abstract

Facilitates chromatin transcription (FACT) is a histone chaperone that supports transcription through chromatin in vitro, but its functional roles in vivo remain unclear. Here, we analyze the in vivo functions of FACT with the use of multi-omics analysis after rapid FACT depletion from human cells. We show that FACT depletion destabilizes chromatin and leads to transcriptional defects, including defective promoter-proximal pausing and elongation, and increased premature termination of RNA polymerase II. Unexpectedly, our analysis revealed that promoter-proximal pausing depends not only on the negative elongation factor (NELF) but also on the +1 nucleosome, which is maintained by FACT.