A differentially methylated single CpG-site is correlated with estrogen receptor alpha transcription

Fürst, Rainer W.; Kliem, H.; Meyer, H. H. D.; Ulbrich, Susanne E.

doi:10.1016/j.jsbmb.2012.01.009

Cited by 51 publications

(38 citation statements)

References 53 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Bisulfite conversion of genomic DNA was performed as previously described [30]. Briefly, 500 ng genomic DNA and the EZ DNA Methylation-Gold Kit (Zymo Research) was used according to the manufacturer’s instructions.…”

Section: Methodsmentioning

confidence: 99%

Hepatic Methionine Homeostasis Is Conserved in C57BL/6N Mice on High-Fat Diet Despite Major Changes in Hepatic One-Carbon Metabolism

et al. 2013

Self Cite

View full text Add to dashboard Cite

Obesity is an underlying risk factor in the development of cardiovascular disease, dyslipidemia and non-alcoholic fatty liver disease (NAFLD). Increased hepatic lipid accumulation is a hallmark in the progression of NAFLD and impairments in liver phosphatidylcholine (PC) metabolism may be central to the pathogenesis. Hepatic PC biosynthesis, which is linked to the one-carbon (C1) metabolism by phosphatidylethanolamine N-methyltransferase, is known to be important for hepatic lipid export by VLDL particles. Here, we assessed the influence of a high-fat (HF) diet and NAFLD status in mice on hepatic methyl-group expenditure and C1-metabolism by analyzing changes in gene expression, protein levels, metabolite concentrations, and nuclear epigenetic processes. In livers from HF diet induced obese mice a significant downregulation of cystathionine β-synthase (CBS) and an increased betaine-homocysteine methyltransferase (BHMT) expression were observed. Experiments in vitro, using hepatoma cells stimulated with peroxisome proliferator activated receptor alpha (PPARα) agonist WY14,643, revealed a significantly reduced Cbs mRNA expression. Moreover, metabolite measurements identified decreased hepatic cystathionine and L-α-amino-n-butyrate concentrations as part of the transsulfuration pathway and reduced hepatic betaine concentrations, but no metabolite changes in the methionine cycle in HF diet fed mice compared to controls. Furthermore, we detected diminished hepatic gene expression of de novo DNA methyltransferase 3b but no effects on hepatic global genomic DNA methylation or hepatic DNA methylation in the Cbs promoter region upon HF diet. Our data suggest that HF diet induces a PPARα-mediated downregulation of key enzymes in the hepatic transsulfuration pathway and upregulates BHMT expression in mice to accommodate to enhanced dietary fat processing while preserving the essential amino acid methionine.

show abstract

Section: Methodsmentioning

confidence: 99%

Hepatic Methionine Homeostasis Is Conserved in C57BL/6N Mice on High-Fat Diet Despite Major Changes in Hepatic One-Carbon Metabolism

et al. 2013

Self Cite

View full text Add to dashboard Cite

show abstract

“…It is well known that the level of cytosine methylation of promoters is negatively correlated with gene expression [71]; the role of methylation of particular CpGs in the regulation of gene expression has been demonstrated in the case of ESR1 [11]. The crucial role of the location of methylated regions relative to TSSs is also widely accepted.…”

Section: Resultsmentioning

confidence: 99%

“…At the same time, methylated CpGs have been found in unmethylated CGIs [4]. It was also shown that a single differentially methylated CpG might affect transcription of the ESR1 gene [11]. Moreover, it was hypothesized that DNA methylation of CpG-rich and CpG-poor regions might be involved in different regulatory programs [12].…”

Section: Introductionmentioning

confidence: 99%

Effects of cytosine methylation on transcription factor binding sites

et al. 2014

View full text Add to dashboard Cite

BackgroundDNA methylation in promoters is closely linked to downstream gene repression. However, whether DNA methylation is a cause or a consequence of gene repression remains an open question. If it is a cause, then DNA methylation may affect the affinity of transcription factors (TFs) for their binding sites (TFBSs). If it is a consequence, then gene repression caused by chromatin modification may be stabilized by DNA methylation. Until now, these two possibilities have been supported only by non-systematic evidence and they have not been tested on a wide range of TFs. An average promoter methylation is usually used in studies, whereas recent results suggested that methylation of individual cytosines can also be important.ResultsWe found that the methylation profiles of 16.6% of cytosines and the expression profiles of neighboring transcriptional start sites (TSSs) were significantly negatively correlated. We called the CpGs corresponding to such cytosines “traffic lights”. We observed a strong selection against CpG “traffic lights” within TFBSs. The negative selection was stronger for transcriptional repressors as compared with transcriptional activators or multifunctional TFs as well as for core TFBS positions as compared with flanking TFBS positions.ConclusionsOur results indicate that direct and selective methylation of certain TFBS that prevents TF binding is restricted to special cases and cannot be considered as a general regulatory mechanism of transcription.

show abstract

“…Nile et al, (2008), reported that methylation status at a single CpG site in the promoter of IL6 affected the regulation of gene expression of IL6, potentially influencing rheumatoid arthritis [38]. In another study, by Fürst et al, (2012), a single differentially methylated CpG was identified to affect transcription of ESR1 [39]. More recently, Dick et al, (2014) identified a single CpG site from whole blood associated with BMI in obese individuals [40].…”

Section: Discussionmentioning

confidence: 99%

Methylome-wide association study of whole blood DNA in the Norfolk Island isolate identifies robust loci associated with age

Benton

Sutherland

Macartney-Coxson

et al. 2017

Aging

View full text Add to dashboard Cite

Epigenetic regulation of various genomic functions, including gene expression, provide mechanisms whereby an organism can dynamically respond to changes in its environment and modify gene expression accordingly. One epigenetic mechanism implicated in human aging and age-related disorders is DNA methylation. Isolated populations such as Norfolk Island (NI) should be advantageous for the identification of epigenetic factors related to aging due to reduced genetic and environmental variation. Here we conducted a methylome-wide association study of age using whole blood DNA in 24 healthy female individuals from the NI genetic isolate (aged 24-47 years). We analysed 450K methylation array data using a machine learning approach (GLMnet) to identify age-associated CpGs. We identified 497 CpG sites, mapping to 422 genes, associated with age, with 11 sites previously associated with age. The strongest associations identified were for a single CpG site in MYOF and an extended region within the promoter of DDO. These hits were validated in curated public data from 2316 blood samples (MARMAL-AID). This study is the first to report robust age associations for MYOF and DDO, both of which have plausible functional roles in aging. This study also illustrates the value of genetic isolates to reveal new associations with epigenome-level data.

show abstract

A differentially methylated single CpG-site is correlated with estrogen receptor alpha transcription

Cited by 51 publications

References 53 publications

Hepatic Methionine Homeostasis Is Conserved in C57BL/6N Mice on High-Fat Diet Despite Major Changes in Hepatic One-Carbon Metabolism

Hepatic Methionine Homeostasis Is Conserved in C57BL/6N Mice on High-Fat Diet Despite Major Changes in Hepatic One-Carbon Metabolism

Effects of cytosine methylation on transcription factor binding sites

Methylome-wide association study of whole blood DNA in the Norfolk Island isolate identifies robust loci associated with age

Contact Info

Product

Resources

About