Nuclear envelope protein MAN1 regulates clock through BMAL1
Shu-Ting Lin,
Luoying Zhang,
Xiaoyan Lin,
Linda Chen Zhang,
Valentina Elizabeth Garcia,
Chen-Wei Tsai,
Louis Ptáček,
Ying-Hui Fu
Affiliations
Shu-Ting Lin
Department of Neurology, University of California, San Francisco, San Francisco, United States
Luoying Zhang
Department of Neurology, University of California, San Francisco, San Francisco, United States
Xiaoyan Lin
Department of Neurology, University of California, San Francisco, San Francisco, United States
Linda Chen Zhang
Department of Neurology, University of California, San Francisco, San Francisco, United States
Valentina Elizabeth Garcia
Department of Neurology, University of California, San Francisco, San Francisco, United States
Chen-Wei Tsai
Department of Neurology, University of California, San Francisco, San Francisco, United States
Louis Ptáček
Department of Neurology, University of California, San Francisco, San Francisco, United States; Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, United States
Ying-Hui Fu
Department of Neurology, University of California, San Francisco, San Francisco, United States
Circadian clocks serve as internal pacemakers that influence many basic homeostatic processes; consequently, the expression and function of their components are tightly regulated by intricate networks of feedback loops that fine-tune circadian processes. 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. We report that transcription of the core clock component BMAL1 is positively modulated by the inner nuclear membrane protein MAN1, which directly binds the BMAL1 promoter and enhances its transcription. 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.
