2. Academic Validation
  3. FACT maintains chromatin architecture and thereby stimulates RNA polymerase II pausing during transcription in vivo

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

  • Mol Cell. 2024 Jun 6;84(11):2053-2069.e9. doi: 10.1016/j.molcel.2024.05.003.
Kristina Žumer 1,  Moritz Ochmann 2,  Abrar Aljahani 3,  Aiturgan Zheenbekova 2,  Arjun Devadas 2,  Kerstin Caroline Maier 2,  Petra Rus 2,  Ute Neef 2,  A Marieke Oudelaar 4,  Patrick Cramer 5
Affiliations

Affiliations

  • 1 Max Planck Institute for Multidisciplinary Sciences, Department of Molecular Biology, Am Fassberg 11, 37077 Göttingen, Germany. Electronic address: [email protected].
  • 2 Max Planck Institute for Multidisciplinary Sciences, Department of Molecular Biology, Am Fassberg 11, 37077 Göttingen, Germany.
  • 3 Max Planck Institute for Multidisciplinary Sciences, Genome Organization and Regulation, Am Fassberg 11, 37077 Göttingen, Germany.
  • 4 Max Planck Institute for Multidisciplinary Sciences, Genome Organization and Regulation, Am Fassberg 11, 37077 Göttingen, Germany. Electronic address: [email protected].
  • 5 Max Planck Institute for Multidisciplinary Sciences, Department of Molecular Biology, Am Fassberg 11, 37077 Göttingen, Germany. Electronic address: [email protected].
PMID: 38810649 DOI: 10.1016/j.molcel.2024.05.003
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.

Keywords

FACT; RNA polymerase II; chromatin; nucleosome; promoter-proximal pausing; transcription.

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