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: To confirm MAN1 regulates the clock by targeting BMAL1, we over-expressed Bmal1 in MAN1 knockdown U2OS Bmal1-Luc cells. Knocking down MAN1 lengthened the period in control cells as described above (Figure 2), whereas cells over-expressing sufficient Bmal1 did not demonstrate period lengthening compared to cells without MAN1 knockdown (Figure 4—figure supplement 2), suggesting that the lengthened period caused by MAN1 deficiency is due to reduction of BMAL1. Together, these results indicate that MAN1 functions to promote BMAL1 expression, and thus exerting effects on the clock.
Affiliation: Department of Neurology, University of California, San Francisco, San Francisco, United States.