Patterns of DNA Methylation Across the Leptin Core Promoter in Four Diverse Asian and North American Populations

DNA methylation is the most widely studied of epigenetic mechanisms, with environmental effects recorded through patterned attachments of methyl groups along the DNA that are capable of modifying gene expression without altering the DNA sequencing. The degree to which these patterns of DNA methylati...

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Bibliographic Details
Published in:Human biology 2016-04, Vol.88 (2), p.121-135
Main Authors: Mosher, M. J., Melton, P. E., Stapleton, P., Schanfield, M. S., Crawford, M. H.
Format: Article
Language:English
Subjects:
Adaptation
Adipogenesis
Adolescent
Adult
Aged
Anthropometry
Archives & records
Asian Continental Ancestry Group - genetics
Binding Sites
Biomarkers
Blood plasma
Bone and Bones - metabolism
CpG Islands
Deoxyribonucleic acid
DNA
DNA Methylation
energy
Epigenesis, Genetic
Epigenetics
Ethnicity
European Continental Ancestry Group - genetics
Famine
Female
Gene expression
Gene expression regulation
Genealogy
Genetic variation
HDL lipoproteins
Homeostasis
Humans
Influence
Integrated approach
leptin
Leptin - chemistry
Leptin - genetics
Leptin - metabolism
Lipids
Male
Mennonite
Metabolism
Methylation
Middle Aged
North America
Nutrigenomics
Physiology
Pilot Projects
Promoter Regions, Genetic
stature
Studies
Young Adult
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Summary:DNA methylation is the most widely studied of epigenetic mechanisms, with environmental effects recorded through patterned attachments of methyl groups along the DNA that are capable of modifying gene expression without altering the DNA sequencing. The degree to which these patterns of DNA methylation are heritable, the expected range of normality across populations, and the phenotypic relevance of pattern variation remain unclear. Genes regulating metabolic pathways appear to be vulnerable to ongoing nutritional programming over the life course, as dietary nutrients are significant environmental determinants of DNA methylation, supplying both the methyl groups and energy to generate the methylation process. Here we examine methylation patterns along a region of the metabolic gene leptin (LEP). LEP's putative functions include regulation of energy homeostasis, with its signals affecting energy intake and expenditure, adipogenesis and energy storage, lipid and glucose metabolism, bone metabolism, and reproductive endocrine function. A pattern of differential methylation across CpG sites of the LEP core promoter has been previously identified; however, any consistency of pattern or its phenotypic significance is not fully elucidated among populations. Using DNA extracted from unfractionated white blood cells of peripheral blood samples, our pilot study, divided into two parts, examined the significance of variation in DNA methylation patterns along the leptin core promoter in four populations (phase 1) and used biomarkers reflecting leptin's functional process in two of those populations, western Buryat of Siberia and the Mennonite of central Kansas, to investigate the relevance of the ethnic variation identified in the DNA methylation (phase 2). LEP's core promoter region contains both the binding site for C/EBPα (CCAAT/enhancer binding protein alpha), which tempers the final step in adipocyte maturity and capacity to synthesize leptin, and the TATA motif controlling leptin synthesis. Previous studies report that increased methylation in this region is correlated to decreased gene expression, suggesting tissue-specific methylation variation at this region (Melzner et al. 2002). We hypothesized that evidence of nutritional epigenetic programming would be identified through variation in patterns of DNA methylation and that functional relevance of that variation among populations would be identified through biomarkers that reflect leptin's metabolic signals: s
ISSN:0018-7143
1534-6617
DOI:10.13110/humanbiology.88.2.0121