RTF1 enhances CLK occupancy and histone methylation at key circadian clock pacemaker gene loci

Nov 4, 2025The Journal of cell biology

RTF1 increases clock protein binding and gene marking at main circadian rhythm genes

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Abstract

Knocking down different subunits of the Drosophila polymerase-associated factor 1 complex (Paf1C) lengthens the circadian locomotion period.

  • Downregulation of rtf1, a core subunit of Paf1C, significantly dampens the amplitude of circadian rhythms.
  • This downregulation is associated with a reduction in the pacemaker protein PERIOD (PER), mediated through decreased per transcription.
  • Overexpression of per in pacemaker neurons can rescue circadian defects caused by rtf1 downregulation.
  • RTF1 enhances CLK-mediated activation of per transcription and physically interacts with CLK.
  • SET1, a methyltransferase, forms a complex with CLK and RTF1, which facilitates their interaction and increases H3K4me3 levels at the per/tim promoter.
  • Human RTF1 interacts with BMAL1/CLOCK and may influence circadian rhythms in mammalian cells.

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