Dataset Information

Ordered changes in histone modifications at the core of the Arabidopsis circadian clock.

ABSTRACT: Circadian clock function in Arabidopsis thaliana relies on a complex network of reciprocal regulations among oscillator components. Here, we demonstrate that chromatin remodeling is a prevalent regulatory mechanism at the core of the clock. The peak-to-trough circadian oscillation is paralleled by the sequential accumulation of H3 acetylation (H3K56ac, K9ac), H3K4 trimethylation (H3K4me3), and H3K4me2. Inhibition of acetylation and H3K4me3 abolishes oscillator gene expression, indicating that both marks are essential for gene activation. Mechanistically, blocking H3K4me3 leads to increased clock-repressor binding, suggesting that H3K4me3 functions as a transition mark modulating the progression from activation to repression. The histone methyltransferase SET DOMAIN GROUP 2/ARABIDOPSIS TRITHORAX RELATED 3 (SDG2/ATXR3) might contribute directly or indirectly to this regulation because oscillator gene expression, H3K4me3 accumulation, and repressor binding are altered in plants misexpressing SDG2/ATXR3. Despite divergences in oscillator components, a chromatin-dependent mechanism of clock gene activation appears to be common to both plant and mammal circadian systems.

SUBMITTER: Malapeira J

PROVIDER: S-EPMC3535592 | biostudies-other | 2012 Dec

REPOSITORIES: biostudies-other

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Ordered changes in histone modifications at the core of the Arabidopsis circadian clock.

Malapeira Jordi J Khaitova Lucie Crhak LC Mas Paloma P

Proceedings of the National Academy of Sciences of the United States of America 20121212 52

Circadian clock function in Arabidopsis thaliana relies on a complex network of reciprocal regulations among oscillator components. Here, we demonstrate that chromatin remodeling is a prevalent regulatory mechanism at the core of the clock. The peak-to-trough circadian oscillation is paralleled by the sequential accumulation of H3 acetylation (H3K56ac, K9ac), H3K4 trimethylation (H3K4me3), and H3K4me2. Inhibition of acetylation and H3K4me3 abolishes oscillator gene expression, indicating that bo ...[more]

PMID: 23236129

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Project description:Objective: Both critical illness and current care have been hypothesized to upset daily rhythms and impair molecular circadian function. However, the influence of critical illness on clock function in different tissues and on circadian output genes are unknown. Here we evaluate the effect of critical care and illness on transcription, focusing on the functional organization of the core circadian oscillator. Methods: We downloaded RNAseq count data from the Genotype-Tissue Expression (GTEx) project. Treating mechanical ventilation as a marker for intensive care, we stratified samples into acute death (AD) and intensive care (IC) groups based on the documented Hardy Death Scale. We restricted our analysis to the 25 tissues with >50 samples in each group. Using the edgeR package and controlling for collection center, gender, and age, we identified transcripts differentially expressed between the AD and IC groups. Overrepresentation and enrichment methods were used to identify gene sets modulated by intensive care across tissues. For each tissue, we then calculated the delta clock correlation distance (ΔCCD), a comparative measure of the functional organization of the core circadian oscillator, in the both the AD and IC groups. The statistical significance of the ΔCCD was assessed by permutation, modifying a pre-existing R package to control for confounding variables. Results: Intensive care, as marked by ventilation, significantly modulated the expression of thousands of genes. Transcripts that were modulated in ≥75% of tissues were enriched for genes involved in mitochondrial energetics, cellular stress, metabolism, and notably circadian regulation. Transcripts that were more markedly affected, in ≥10 tissues, were enriched for inflammation, complement and immune pathways. Oscillator organization, as assessed by ΔCCD, was significantly reduced in the intensive care group in 11/25 tissues. Conclusion: Our findings support the hypothesis that patients in intensive care have impaired molecular circadian rhythms. Tissues involved in metabolism and energetics demonstrated the most marked changes in oscillator organization. In adipose tissue, there was a significant overlap between transcripts previously established to be modulated by sleep deprivation and fasting with those modulated by critical care. This work suggests that intensive care protocols that restore sleep/wake and nutritional rhythms may be of benefit.

Dataset Information

Ordered changes in histone modifications at the core of the Arabidopsis circadian clock.

Publications

Ordered changes in histone modifications at the core of the Arabidopsis circadian clock.

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