title: Nuclear envelope protein MAN1 regulates clock through BMAL1.
abstract: 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.
authors.affiliation: Department of Neurology, University of California, San Francisco, San Francisco, United States.
authors.forename: Shu-Ting
authors.initials: ST
authors.lastname: Lin
authors.affiliation: Department of Neurology, University of California, San Francisco, San Francisco, United States.
authors.forename: Luoying
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Neurology, University of California, San Francisco, San Francisco, United States.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Lin
authors.affiliation: Department of Neurology, University of California, San Francisco, San Francisco, United States.
authors.forename: Linda Chen
authors.initials: LC
authors.lastname: Zhang
authors.affiliation: Department of Neurology, University of California, San Francisco, San Francisco, United States.
authors.forename: Valentina Elizabeth
authors.initials: VE
authors.lastname: Garcia
authors.affiliation: Department of Neurology, University of California, San Francisco, San Francisco, United States.
authors.forename: Chen-Wei
authors.initials: CW
authors.lastname: Tsai
authors.affiliation: 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.
authors.forename: Louis
authors.initials: L
authors.lastname: Ptáček
authors.affiliation: Department of Neurology, University of California, San Francisco, San Francisco, United States ying-hui.fu@ucsf.edu.
authors.forename: Ying-Hui
authors.initials: YH
authors.lastname: Fu
mesh_terms: D056930:ARNTL Transcription Factors / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western; D045744:Cell Line, Tumor; D057906:Circadian Clocks / Q000235:genetics*; D004268:DNA-Binding Proteins; D005786:Gene Expression Regulation; D057809:HEK293 Cells; D006801:Humans; D034921:Lamin Type B / Q000235:genetics / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009685:Nuclear Envelope / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D056930:ARNTL Transcription Factors; C538960:BMAL1 protein, human; D004268:DNA-Binding Proteins; C405329:LEMD3 protein, human; D034921:Lamin Type B; D008565:Membrane Proteins; D009687:Nuclear Proteins
keywords: BMAL1; MAN1; circadian rhythm; nuclear envelope