Molecular and epigenetic regulation of biological clocks
Our lab studies molecular and epigenetic pathways that control biological oscillators, especially those that help establish and operate mammalian circadian clocks. Of the many epigenetic regulators, we are particularly interested in histone variants – key factors that control transcriptional outputs by regulating chromatin structure. Both physiological and pathological aging coincides with a loss in robustness of circadian oscllators and chromatin state. With this in mind, we are interested in understanding:
Figure 1. Circadian expression of the Rev-Luc transgene in mice by bioluminescence imaging. Left, representative luminescent imaging of the same anesthetized Rev-Luc reporter transgenic mice over time for the ventral and dorsal faces.
Right, quantitative bioluminescence radiance as a function of zeitgeber time for ventral (n=34) and dorsal (n=15) expositions. The fitted dark line represents the mean cosine wave of best fit with a 24 h period. (Canaple et al, Unpublished).
Figure 2: Real-time bioluminescence from control U2OS cells expressing a Bmal1-Luc reporter over 5 days in culture.
Current lab members:
Laurence Canaple (IR, CNRS)
Helene Boyer (PhD, ENS)
Eric Folco (Postdoc)
Nicolas McAdams (M2 stagiare)
Lies Chikhaoui (M1 stagiare)
Shannin Arenale Castillo (M1)
Isahak Saidi (M2)
1. Roulland Y , Ouararhni K , Naidenov M , Ramos L , Shuaib M , Syed SH , Lone IN, Boopathi R, Fontaine E , Papai G ,Tachiwana H, Gautier T , Skoufias D , Padmanabhan K , Bednar J , Kurumizaka H, Schultz P, Angelov D , Hamiche A & Dimitrov S. The flexible ends of CENP-A nucleosome are required for mitotic fidelity. Molecular Cell. 32081-7(16). 2016.
2. Obri A, Ouararhni K, Papin C, Diebold ML, Padmanabhan K, Marek M, Stoll I, Roy L, Reilly PT, Mak TW, Dimitrov S, Romier C and Hamiche A. ANP32E is a histone chaperone that removes H2A.Z from chromatin. Nature. 505: 648-53. 2014
3. Padmanabhan K, Robles M, Westerling T and Weitz CJ. Feedback regulation of transcriptional termination by the mammalian circadian clock PERIOD complex. Science. 337: 599-602. 2012
4. Robles M, Boyault C, Knutti D, Padmanabhan K and Weitz CJ. Identification of RACK1 and protein kinase Calpha as integral components of the mammalian circadian clock. Science. 327: 463-6, 2010.
Postdocs and students who are interested in joining the lab should send:
kiran.padmanabhan @ ens-lyon.fr
The lab's research benefits from funding from: