PT  - JOURNAL ARTICLE
AU  - Litovchenko, Maria
AU  - Meireles-Filho, Antonio C. A.
AU  - Frochaux, Michael V.
AU  - Bevers, Roel P. J.
AU  - Prunotto, Alessio
AU  - Anduaga, Ane Martin
AU  - Hollis, Brian
AU  - Gardeux, Vincent
AU  - Braman, Virginie S.
AU  - Russeil, Julie M. C.
AU  - Kadener, Sebastian
AU  - dal Peraro, Matteo
AU  - Deplancke, Bart
TI  - Extensive tissue-specific expression variation and novel regulators underlying circadian behavior
AID  - 10.1126/sciadv.abc3781
DP  - 2021 Jan 01
TA  - Science Advances
PG  - eabc3781
VI  - 7
IP  - 5
4099  - http://advances.sciencemag.org/content/7/5/eabc3781.short
4100  - http://advances.sciencemag.org/content/7/5/eabc3781.full
SO  - Sci Adv2021 Jan 01; 7
AB  - 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 Drosophila melanogaster (w1118) and 141 Drosophila 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 cry 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.