The Paralogous Krüppel-like Factors 9 and 13 Regulate the Mammalian Cellular Circadian Clock Output Gene Dbp

Of the 3514 KLF9 peaks identified in HT22 cells, 1028 contain E-box sequences that may bind transcriptional activators.

• KLF9 is regulated by a transcription-translation feedback loop that governs circadian rhythms in mammals.
• KLF9 associates with chromatin at core circadian clock and clock-output genes, influencing their transcription.
• Circadian oscillation of mRNA was observed in synchronized HT22 cells, mouse hippocampus, and liver.
• Forced expression of KLF9 in HT22 cells repressed basal transcription and inhibited CLOCK+BMAL1-dependent activation.
• Knockout of KLF9 and its paralog KLF13 using CRISPR/Cas9 impaired circadian mRNA oscillation in HT22 cells.
• KLF13 also associates with clock genes and its expression inhibits CLOCK+BMAL1 transcriptional actions.

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