Extensive tissue-specific expression variation and novel regulators underlying circadian behavior

Natural genetic variation affects circadian rhythms across the evolutionary tree, but the underlying molecular mechanisms are poorly understood. We investigated population-level, molecular circadian clock variation by generating >700 tissue-specific transcriptomes of ( ) and 141 Genetic Reference...

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Veröffentlicht in:Science advances 2021-01, Vol.7 (5)
Hauptverfasser: Litovchenko, Maria, Meireles-Filho, Antonio C A, Frochaux, Michael V, Bevers, Roel P J, Prunotto, Alessio, Anduaga, Ane Martin, Hollis, Brian, Gardeux, Vincent, Braman, Virginie S, Russeil, Julie M C, Kadener, Sebastian, Dal Peraro, Matteo, Deplancke, Bart
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Sprache:eng
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Zusammenfassung:Natural genetic variation affects circadian rhythms across the evolutionary tree, but the underlying molecular mechanisms are poorly understood. We investigated population-level, molecular circadian clock variation by generating >700 tissue-specific transcriptomes of ( ) and 141 Genetic Reference Panel (DGRP) lines. This comprehensive circadian gene expression atlas contains >1700 cycling genes including previously unknown central circadian clock components and tissue-specific regulators. Furthermore, >30% of DGRP lines exhibited aberrant circadian gene expression, revealing abundant genetic variation-mediated, intertissue circadian expression desynchrony. Genetic analysis of one line with the strongest deviating circadian expression uncovered a novel mutation that, as shown by protein structural modeling and brain immunohistochemistry, disrupts the light-driven flavin adenine dinucleotide cofactor photoreduction, providing in vivo support for the importance of this conserved photoentrainment mechanism. Together, our study revealed pervasive tissue-specific circadian expression variation with genetic variants acting upon tissue-specific regulatory networks to generate local gene expression oscillations.
ISSN:2375-2548
2375-2548
DOI:10.1126/sciadv.abc3781