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Biochim Biophys Acta. 2014 Sep;1839(9):866-72. doi: 10.1016/j.bbagrm.2014.07.011. Epub 2014 Jul 18.

The role of H3K4me3 and H3K9/14ac in the induction by dexamethasone of Per1 and Sgk1, two glucocorticoid [corrected] early response genes that mediate the effects of acute stress in mammals.

Author information

1
Laboratory of Nuclear Proteins and Chromatin Function, Institute of Biosciences and Applications, National Center for Scientific Research "DEMOKRITOS", P.O.B. 60037, Aghia Paraskevi, 153 10 Attiki, Greece. Electronic address: m_xydous@yahoo.com.
2
Laboratory of Chronobiology, Institute of Biosciences and Applications, National Center for Scientific Research "DEMOKRITOS", P.O.B. 60037, Aghia Paraskevi, 153 10 Attiki, Greece. Electronic address: prombona@bio.demokritos.gr.
3
Laboratory of Nuclear Proteins and Chromatin Function, Institute of Biosciences and Applications, National Center for Scientific Research "DEMOKRITOS", P.O.B. 60037, Aghia Paraskevi, 153 10 Attiki, Greece. Electronic address: sourlin@bio.demokritos.gr.

Abstract

Glucocorticoids are known to induce or repress the expression of a wide variety of genes with roles in various biological processes such as the circadian clock and the stress response. We studied the changes in the levels of two histone H3 post-translational modifications associated with active chromatin, H3 trimethylated at lysine 4 (H3K4me3) and H3 acetylated at lysines 9/14 (H3K9/14ac), that take place in the promoters of two glucocorticoid early response genes, Per1 and Sgk1, during their induction by the synthetic glucocorticoid, dexamethasone. Sgk1 mediates the effects of acute and chronic stress on the prefrontal cortex and other parts of the brain, while Per1 is a core circadian clock gene whose expression is strongly induced by the increased levels of blood-borne glucocorticoids that accompany acute and chronic stress. Here we show that dexamethasone rapidly increases the levels of H3K4me3 and H3K9/14ac in the promoters of both genes. Furthermore, the effect of dexamethasone on these genes, regarding both mRNA levels and the abundance of H3K4me3 and H3K9/14ac in their promoters, can be inhibited by the presence of nicotinamide, a metabolic molecule which has been shown to possess anxiolytic properties.

KEYWORDS:

Acute stress; Glucocorticoid early response gene; Histone H3 post-translational modification; Nicotinamide; Per1 core clock gene; Sgk1

PMID:
25046865
DOI:
10.1016/j.bbagrm.2014.07.011
[Indexed for MEDLINE]

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