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KAP1 negatively regulates RNA polymerase II elongation kinetics to activate signal-induced transcription

Nature Communications, ISSN: 2041-1723, Vol: 15, Issue: 1, Page: 5859
2024
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  • 11
    Captures
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    Mentions
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  • Captures
    11
  • Mentions
    1
    • News Mentions
      1
      • News
        1

Most Recent News

Reports from University of Texas Southwestern Medical Center Add New Data to Research in DNA-Directed DNA Polymerase (KAP1 negatively regulates RNA polymerase II elongation kinetics to activate signal-induced transcription)

2024 JUL 29 (NewsRx) -- By a News Reporter-Staff News Editor at NewsRx Life Science Daily -- Investigators discuss new findings in DNA-directed DNA polymerase.

Article Description

Signal-induced transcriptional programs regulate critical biological processes through the precise spatiotemporal activation of Immediate Early Genes (IEGs); however, the mechanisms of transcription induction remain poorly understood. By combining an acute depletion system with several genomics approaches to interrogate synchronized, temporal transcription, we reveal that KAP1/TRIM28 is a first responder that fulfills the temporal and heightened transcriptional demand of IEGs. Acute KAP1 loss triggers an increase in RNA polymerase II elongation kinetics during early stimulation time points. This elongation defect derails the normal progression through the transcriptional cycle during late stimulation time points, ultimately leading to decreased recruitment of the transcription apparatus for re-initiation thereby dampening IEGs transcriptional output. Collectively, KAP1 plays a counterintuitive role by negatively regulating transcription elongation to support full activation across multiple transcription cycles of genes critical for cell physiology and organismal functions.

Bibliographic Details

Hyder, Usman; Challa, Ashwini; Thornton, Micah; Nandu, Tulip; Kraus, W Lee; D'Orso, Iván

Springer Science and Business Media LLC

Chemistry; Biochemistry, Genetics and Molecular Biology; Physics and Astronomy

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