Abstract

Methyl CpG binding protein 2 (MeCP2) is a chromosomal protein of the brain, very abundant especially in neurons, where it plays an important role in the regulation of gene expression. Hence it has the potential to be affected by the mammalian circadian cycle. We performed expression analyses of mice brain frontal cortices obtained at different time points and we found that the levels of MeCP2 are altered circadianly, affecting overall organization of brain chromatin and resulting in a circadian-dependent regulation of well-stablished MeCP2 target genes. Furthermore, this data suggests that alterations of MeCP2 can be responsible for the sleeping disorders arising from pathological stages, such as in autism and Rett syndrome.

Highlights

  • Many physiological aspects of a wide range of organisms, from cyanobacteria to mammals, display circadian oscillations as a mechanism to adapt to the 24 hours light-dark cycles [1,2,3].In mammals, the central biological clock is found in the suprachiasmatic nucleus (SCN) of the hypothalamus, light being the main environmental stimulus capable of resetting the clock

  • We investigated the micrococcal nuclease (MNase) accessibility to promoter regions of three known Methyl CpG binding protein 2 (MeCP2) target genes, brain derived neurotrophic factor (Bdnf), delta-like 1 homolog (Dlk1), and somatostatin (Sst) [19, 30]

  • The results showed that Bdnf as well as Dlk1 and Sst displayed in all instances circadian patterns of expression (Fig 3A) in a similar way as the MeCP2 variation (Fig 1) and MNase doi:10.1371/journal.pone.0123693.g003

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Summary

Introduction

Many physiological aspects of a wide range of organisms, from cyanobacteria to mammals, display circadian oscillations as a mechanism to adapt to the 24 hours light-dark cycles [1,2,3]. The central biological clock is found in the suprachiasmatic nucleus (SCN) of the hypothalamus, light being the main environmental stimulus capable of resetting the clock. The retina receives the light signals and sends this information through the retinohypothalamic tract to the SCN, which in turn synchronizes peripheral clocks present in most organs [2], reviewed in [4]. When the oligomeric CRY and PER proteins associate, they enter the nucleus and inhibit BMAL1 and CLOCK transcriptional activity, repressing their own transcription [2, 7]

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