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Related Experiment Videos

NPAS2: a gas-responsive transcription factor.

Elhadji M Dioum1, Jared Rutter, Jason R Tuckerman

  • 1Departments of Biochemistry and Plant Biology and Plant Biotechnology Center, The Ohio State University, 1060 Carmack Road, Columbus, OH 43210, USA.

Science (New York, N.Y.)
|November 26, 2002
PubMed
Summary
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Neuronal PAS domain protein 2 (NPAS2) binds heme, a molecule that regulates its DNA binding. Carbon monoxide disrupts NPAS2-BMAL1 heterodimers, impacting circadian rhythm gene expression.

Area of Science:

  • Molecular Biology
  • Chronobiology
  • Biochemistry

Background:

  • Neuronal PAS domain protein 2 (NPAS2) is a transcription factor crucial for circadian rhythm regulation.
  • NPAS2 functions as a heterodimer with BMAL1, binding DNA to control gene expression.

Purpose of the Study:

  • To investigate the role of heme in NPAS2 function.
  • To elucidate the mechanism by which heme status and gaseous molecules affect NPAS2-BMAL1 DNA binding and circadian regulation.

Main Methods:

  • In vitro DNA binding assays were performed using NPAS2-BMAL1 heterodimers in apo (heme-free) and holo (heme-loaded) states.
  • The effect of varying ratios of NADP(H) and carbon monoxide (CO) on DNA binding was assessed.

Main Results:

Related Experiment Videos

  • Both PAS domains of NPAS2 bind heme, which modulates DNA binding activity.
  • Heme-loaded NPAS2-BMAL1 heterodimers showed avid DNA binding under specific reducing conditions.
  • Carbon monoxide inhibited holo-NPAS2 DNA binding and promoted BMAL1 homodimer formation, disrupting NPAS2-BMAL1 heterodimers.

Conclusions:

  • Heme acts as a prosthetic group in NPAS2, sensing and integrating cellular redox and gaseous signals.
  • The NPAS2-BMAL1 heterodimerization and subsequent gene regulation are controlled by heme-based gas sensing, providing a novel regulatory mechanism for circadian rhythm.