Nuclear envelope protein MAN1 regulates clock through BMAL1.
Bottom Line: Our knowledge of these components and pathways is far from exhaustive.In recent decades, the nuclear envelope has emerged as a global gene regulatory machine, although its role in circadian regulation has not been explored.Our results establish a novel connection between the nuclear periphery and circadian rhythmicity, therefore bridging two global regulatory systems that modulate all aspects of bodily functions.
Affiliation: Department of Neurology, University of California, San Francisco, San Francisco, United States.Show MeSH
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Mentions: A luciferase reporter assay using HEK293 cells was used to further investigate the effect of MAN1 on BMAL1 transcription. MAN1 knockdown decreased Bmal1-Luc activity by 72% (Figure 6A), whereas overexpression of FLAG-MAN1 increased the luciferase activity by more than twofold vs cells transfected with empty vector (Figure 6B). Similar results were obtained with a longer, human BMAL1 promoter (Figure 6C). These data indicate that MAN1 may play a role in circadian regulation by activating the promoter of BMAL1.10.7554/eLife.02981.016Figure 6.MAN1 promotes BMAL1 transcriptional activity.
Affiliation: Department of Neurology, University of California, San Francisco, San Francisco, United States.