Epigenetics and the control of epithelial sodium channel expression in collecting duct.
Kidney Int. 2008 Sep 24. [Epub ahead of print]
Zhang D, Yu ZY, Cruz P, Kong Q, Li S, Kone BC.
1Division of Nephrology, Hypertension and Renal Transplantation, University of Florida College of Medicine, Gainesville, Florida, USA.
In eukaryotic nuclei, genomic DNA is compacted with histone and nonhistone proteins into a dynamic polymer termed chromatin. Reorganization of chromatin structure through histone modifications, the action of chromatin factors, or DNA methylation, can profoundly change gene expression. These epigenetic modifications allow heritable and potentially reversible changes in gene functioning to occur without altering the DNA sequence, thus extending the information potential of the genetic code. This review provides an introduction to epigenetic concepts for renal investigators and an overview of our work detailing an epigenetic pathway for aldosterone signaling and the control of epithelial Na(+) channel-alpha (ENaCalpha) subunit gene expression in the collecting duct. This new pathway involves a nuclear repressor complex, consisting of histone H3 Lys-79 methyltransferase disruptor of telomeric silencing-1a (Dot1a), ALL1 fused gene from chromosome 9 (Af9), a sequence-specific DNA-binding protein that binds the ENaCalpha promoter, and potentially other nuclear proteins. This complex regulates targeted histone H3 Lys-79 methylation of chromatin associated with the ENaCalpha promoter, thereby suppressing its transcriptional activity. Aldosterone disrupts the Dot1a-Af9 interaction by serum- and glucocorticoid-induced kinase-1 phosphorylation of Af9, and inhibits Dot1a and Af9 expression, resulting in histone H3 Lys-79 hypomethylation at specific subregions, and derepression of the ENaCalpha promoter. The Dot1a-Af9 pathway may also be involved in the control of genes implicated in renal fibrosis and hypertension.Kidney International advance online publication, 24 September 2008; doi:10.1038/ki.2008.475.
PMID: 18818687 [PubMed - as supplied by publisher]
Monday, November 10, 2008
The evaluation of level of epigenetic indicator--5-methylcytosine in smoking and non-smoking patients with mild essential hypertension.
The evaluation of level of epigenetic indicator--5-methylcytosine in smoking and non-smoking patients with mild essential hypertension.
Przegl Lek. 2007;64(10):695-7.
Smolarek I, Olszewski J, Naskret-Barciszewska M, Wyszko E, Jabłecka A.
Zaktad Farmakologii Klinicznej, Katedry Kardiologii, Uniwersytetu Medycznego im. K. Marcinkowskiego w Poznaniu. iwosmo@wp.pl
5-methylcytosine (m5C, 5mC) is a nucleotide occurring naturally in genomic DNA and play an important role in regulation of genes expression. Methylation of cytosine in DNA is an epigenetic modification and different intrinsic and extrinsic factors can influence on its level. For example, it is subject to modification and/or degradation by the free radicals which are commonly present in environment of human, among others the cigarette smoke. The reactions of m5C with free radicals lead to origination of many products which effect is decrease of level of m5C in DNA (hypomethylation) and excessive expression of genes inducing development of different diseases, especially cardiovascular system diseases. The aim of the study was statement if exist differences of level of 5-methylcytosine in DNA between smoking and non-smoking patients suffering from mild essential hypertension. The study group was composed of 30 patients suffering from mild essential hypertension (21 females and 40 males) aged from 18 to 55 years (32.4+/-10.3 years). The group of smoker was composed of 13 patients (5 females and 8 males) and the group of non-smokers was composed of 17 patients (7 females and 10 males). 3-5 ml of blood was sampled on EDTA and then thin-layer chromatography analysis of 5-methylcytosine level in DNA after previous enzymatic hydrolysis of DNA and radioactive phosphorus labeling [32p] was performed. The mean level of 5-methylcytosine (m5C) were 1.30+/-0.56 [%] in non-smoking patients, and 1.28+/-0.42 [%] in smoking patients suffering from mild essential hypertension. There is no significant statistically differences between non-smoking and smoking patients (p>0.4). In the study the following conclusion was drawn: the level of m5C in DNA of patients suffering from mild essential hypertension in the study is independent of smoking (p>0.4) in patients with mild essential hypertension. However it supposes, out of regard for theoretic datum suggestive such influence, the study should be performed in more frequent group of patients.
PMID: 18409288 [PubMed - indexed for MEDLINE]
Przegl Lek. 2007;64(10):695-7.
Smolarek I, Olszewski J, Naskret-Barciszewska M, Wyszko E, Jabłecka A.
Zaktad Farmakologii Klinicznej, Katedry Kardiologii, Uniwersytetu Medycznego im. K. Marcinkowskiego w Poznaniu. iwosmo@wp.pl
5-methylcytosine (m5C, 5mC) is a nucleotide occurring naturally in genomic DNA and play an important role in regulation of genes expression. Methylation of cytosine in DNA is an epigenetic modification and different intrinsic and extrinsic factors can influence on its level. For example, it is subject to modification and/or degradation by the free radicals which are commonly present in environment of human, among others the cigarette smoke. The reactions of m5C with free radicals lead to origination of many products which effect is decrease of level of m5C in DNA (hypomethylation) and excessive expression of genes inducing development of different diseases, especially cardiovascular system diseases. The aim of the study was statement if exist differences of level of 5-methylcytosine in DNA between smoking and non-smoking patients suffering from mild essential hypertension. The study group was composed of 30 patients suffering from mild essential hypertension (21 females and 40 males) aged from 18 to 55 years (32.4+/-10.3 years). The group of smoker was composed of 13 patients (5 females and 8 males) and the group of non-smokers was composed of 17 patients (7 females and 10 males). 3-5 ml of blood was sampled on EDTA and then thin-layer chromatography analysis of 5-methylcytosine level in DNA after previous enzymatic hydrolysis of DNA and radioactive phosphorus labeling [32p] was performed. The mean level of 5-methylcytosine (m5C) were 1.30+/-0.56 [%] in non-smoking patients, and 1.28+/-0.42 [%] in smoking patients suffering from mild essential hypertension. There is no significant statistically differences between non-smoking and smoking patients (p>0.4). In the study the following conclusion was drawn: the level of m5C in DNA of patients suffering from mild essential hypertension in the study is independent of smoking (p>0.4) in patients with mild essential hypertension. However it supposes, out of regard for theoretic datum suggestive such influence, the study should be performed in more frequent group of patients.
PMID: 18409288 [PubMed - indexed for MEDLINE]
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