Joined the Department in 2013
- B.Sc., 1996, Sciences and Technology University of Lille (Lille, France), Molecular and Cellular Biology
- M.Sc., 1999, Louis Pasteur University (Strasbourg, France), Neurosciences
- Ph.D., 2003, Louis Pasteur University (Strasbourg, France), Neurosciences
- Postdoctoral Research, Brandeis University
Center for Biological Clocks Research
Molecular Underpinnings of the Circadian Clock in Mouse
Most organisms from bacteria to humans exhibit 24-hours rhythms in their biochemistry, physiology and behavior. Best exemplified by the sleep/wake cycle, these rhythms are remarkably widespread and include in humans hormonal (e.g., melatonin, insulin, cortisol), metabolic (e.g., glucose, cholesterol), physiological and behavioral oscillations. In fact, most biological functions are rhythmic and are set to perform optimally at the most appropriate time of the day. For example, the human digestion process performs better during the day when we are supposed to eat.
These circadian rhythms are generated by “molecular clocks”, which consist of a few “clock genes” interacting in feedback loops, and which drive the rhythmic expression of a large number of genes, i.e. ~10% of the transcriptome in any tissues. This wide impact of clock genes in regulating gene expression is underscored by the surprisingly large number of pathologies developed by clock-deficient mice. In addition to being arrhythmic, these mice indeed develop pathologies as diverse as mania-like behaviors, learning and memory defects, depression, drug addiction, insomnia, metabolic diseases, arthropathy, hematopoiesis defects and cancers.
Research in our lab aims at characterizing how circadian clocks and clock genes regulate gene expression to provide insights into how and why clock dysfuntion leads to a wide spectra of pathologies. To this end, we are using a wide-range of molecular and biochemical techniques to investigate the circadian clock function at the genome-wide level (e.g., next-generation sequencing). We are currently extending some of our recent results and focus on 1) how clock genes rhythmically regulate chromatin environment and 2) the mechanisms involved in rhythmic post-transcriptional regulation of gene expression.
- Trott, AJ, Greenwell, BJ, Karhadkar, TR, Guerrero-Vargas, NN, Escobar, C, Buijs, RM et al.. Lack of food intake during shift work alters the heart transcriptome and leads to cardiac tissue fibrosis and inflammation in rats. BMC Biol. 2022;20 (1):58. doi: 10.1186/s12915-022-01256-9. PubMed PMID:35236346 PubMed Central PMC8892784.
- Zhang, Y, Iiams, SE, Menet, JS, Hardin, PE, Merlin, C. TRITHORAX-dependent arginine methylation of HSP68 mediates circadian repression by PERIOD in the monarch butterfly. Proc Natl Acad Sci U S A. 2022;119 (4):. doi: 10.1073/pnas.2115711119. PubMed PMID:35064085 PubMed Central PMC8795551.
- Beytebiere, JR, Greenwell, BJ, Sahasrabudhe, A, Menet, JS. Clock-controlled rhythmic transcription: is the clock enough and how does it work?. Transcription. 2019;10 (4-5):212-221. doi: 10.1080/21541264.2019.1673636. PubMed PMID:31595813 PubMed Central PMC6948975.
- Lugena, AB, Zhang, Y, Menet, JS, Merlin, C. Genome-wide discovery of the daily transcriptome, DNA regulatory elements and transcription factor occupancy in the monarch butterfly brain. PLoS Genet. 2019;15 (7):e1008265. doi: 10.1371/journal.pgen.1008265. PubMed PMID:31335862 PubMed Central PMC6677324.
- Greenwell, BJ, Trott, AJ, Beytebiere, JR, Pao, S, Bosley, A, Beach, E et al.. Rhythmic Food Intake Drives Rhythmic Gene Expression More Potently than the Hepatic Circadian Clock in Mice. Cell Rep. 2019;27 (3):649-657.e5. doi: 10.1016/j.celrep.2019.03.064. PubMed PMID:30995463 .
- Beytebiere, JR, Trott, AJ, Greenwell, BJ, Osborne, CA, Vitet, H, Spence, J et al.. Tissue-specific BMAL1 cistromes reveal that rhythmic transcription is associated with rhythmic enhancer-enhancer interactions. Genes Dev. 2019;33 (5-6):294-309. doi: 10.1101/gad.322198.118. PubMed PMID:30804225 PubMed Central PMC6411008.
- Trott, AJ, Menet, JS. Regulation of circadian clock transcriptional output by CLOCK:BMAL1. PLoS Genet. 2018;14 (1):e1007156. doi: 10.1371/journal.pgen.1007156. PubMed PMID:29300726 PubMed Central PMC5771620.
- Hughes, ME, Abruzzi, KC, Allada, R, Anafi, R, Arpat, AB, Asher, G et al.. Guidelines for Genome-Scale Analysis of Biological Rhythms. J Biol Rhythms. 2017;32 (5):380-393. doi: 10.1177/0748730417728663. PubMed PMID:29098954 PubMed Central PMC5692188.
- Lerner, I, Bartok, O, Wolfson, V, Menet, JS, Weissbein, U, Afik, S et al.. Clk post-transcriptional control denoises circadian transcription both temporally and spatially. Nat Commun. 2015;6 :7056. doi: 10.1038/ncomms8056. PubMed PMID:25952406 PubMed Central PMC4915573.
- Menet, JS, Hardin, PE. Circadian clocks: the tissue is the issue. Curr Biol. 2014;24 (1):R25-R27. doi: 10.1016/j.cub.2013.11.016. PubMed PMID:24405673 PubMed Central PMC4157344.