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Institute of Pharmacology and Toxicology Chronobiology and Sleep Research

Project 3: Epigenetic mechanisms regulating circadian behavior

Abdelhalim Azzi

It is well known that the circadian clock is partially controlled by genetic factors. For example, twin studies suggested that human diurnal behavior is 50-60% heritable [1]. However, environmental effects on circadian behavior have received little attention. Previous studies have shown that entrainment to light/dark cycles longer or shorter than 24 hours can result in long-lasting changes of the endogenous free-running period (FRP) [2]. The mechanisms driving such plasticity are unknown. In other fields of research, it was found that early life environmental change induces changes in the DNA methylation pattern of the genome [3-4]. This epigenetic modification involves the addition of a methyl group to the 5’ position of cytosine nucleotides. DNA methylation stably alters the transcription without altering gene sequence. Given that this modification is highly dynamic during development, and it can be influenced directly by environmental modifications [5], we wanted to investigate its role in determining circadian clock properties. This project focuses on how early-life lighting environment affects circadian behavior and epigenetic properties of the SCN, and how these changes affect the network properties of the SCN neurons.

Methods used

Behavior analysis
Whole genome DNA methylation analysis (Microarray)
Targeted DNA methylation analysis (sequencing approach)
Transcriptomic analysis. SCN slice culture


1. Koskenvuo, M., Hublin, C., Partinen, M., Heikkila, K. and Kaprio, J. Heritability of diurnal type: a nationwide study of 8753 adult twin pairs. J Sleep Res 16, 156-62. (2007)

2. Pittendrigh C.S, Daan. S. A. a functional analysis of circadian pacemakers in nocturnal rodents. I. The stability and lability of circadian frequency. J Comp Physiol A 106, 223-252 (1976).

3. Chris Murgatroyd, Alexandre V Patchev, Yonghe Wu, Vincenzo Micale, Yvonne Bockmühl, Dieter Fischer, Florian Holsboer, Carsten T Wotjak, Osborne F X Almeida and Dietmar Spengler. Dynamic DNA methylation programs persistent adverse effects of early-life stress Nat Neurosci 12, 1559 - 1566 (2009)

4. Courtney A. Miller and J. David Sweatt. Covalent Modification of DNA Regulates Memory Formation. Neuron 6, 857-869 (2007)

5. Rudolf Jaenisch and Adrian Bird. Epigenetic regulation of gene expression: how the genome integrates intrinsic and environmental signals. Nature Genetics 33, 245 - 254 (2003)  


Weiterführende Informationen


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