Login / Signup

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

Maria LitovchenkoAntonio C A Meireles-FilhoMichael V FrochauxRoel P J BeversAlessio PrunottoAne Martin AnduagaBrian HollisVincent GardeuxVirginie S BramanJulie M C RusseilSebastian KadenerMatteo Dal PeraroBart Deplancke
Published in: Science advances (2021)
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.
Keyphrases
  • gene expression
  • poor prognosis
  • genome wide
  • dna methylation
  • transcription factor
  • binding protein
  • drosophila melanogaster
  • single cell
  • long non coding rna
  • brain injury
  • blood brain barrier
  • subarachnoid hemorrhage