cAMP-response Element (CRE)-mediated transcription by Activating Transcription Factor-4 (ATF4) is essential for circadian expression of the Period2 gene

Satoru Koyanagi, Ahmed M. Hamdan, Michiko Horiguchi, Naoki Kusunose, Akinori Okamoto, Naoya Matsunaga, Shigehiro Ohdo

Research output: Contribution to journalArticlepeer-review

56 Citations (Scopus)

Abstract

Activating transcription factor (ATF)/cAMP-response element (CRE)-binding (CREB) proteins induce the CRE-mediated gene transcription depending on the cAMP stimulation. cAMP-dependent signaling oscillates in a circadian manner, which in turn also sustains core oscillation machinery of the circadian clock. Here, we show that among the ATF/CREB family proteins, ATF4 is essential for the circadian expression of the Period2 (Per2) gene, a key component of the circadian clock. Transcription of the Atf4 gene was regulated by core components of the circadian clock, and its expression exhibited circadian oscillation in mouse tissues as well as embryonic fibroblasts. ATF4 bound to the CRE of the Per2 promoter in a circadian time-dependent manner and periodically activated the transcription of the Per2 gene. Consequently, the oscillation of the Per2 expression was attenuated in embryonic cells prepared from Atf4-null mice. Furthermore, the loss of ATF4 also disrupted the rhythms in the expression of other clock genes. These results suggest that ATF4 is a component responsible for sustaining circadian oscillation of CRE-mediated gene expression and also constitute a molecular link connecting cAMP-dependent signaling to the circadian clock.

Original languageEnglish
Pages (from-to)32416-32423
Number of pages8
JournalJournal of Biological Chemistry
Volume286
Issue number37
DOIs
Publication statusPublished - Sep 16 2011

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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