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


ABSTRACT: 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.

SUBMITTER: Litovchenko M 

PROVIDER: S-EPMC7846174 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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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 <i>Drosophila melanogaster</i> (<i>w<sup>1118</sup></i> ) and 141 <i>Drosophila</i> Genetic Reference Panel (DGRP) lines. This comprehensive circadian gene expression atlas contains >1700 cycling genes including previously unknown c  ...[more]

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