Placental methylation and pro-inflammatory protein levels in cord blood.

Introduction: The neonates' inflammatory response may in part be shaped during development by the placental epigenome, but evidence is scarce. We investigated the association between placental DNA methylation and pro-inflammatory proteins in cord blood.

Methods: A total of 249 mother-child dyads from the Harvard Epigenetic Birth Cohort were included in this study.

The impact of pre-pregnancy folic acid intake on placental DNA methylation in a fortified cohort.

Folate plays an important role in the modulation of one-carbon metabolism and DNA methylation through a complex biosynthesis pathway. Folate deficiency during pregnancy has been associated with an increased risk for birth defects. This study investigates the extent to which the availability of folate and S-Adenosylmethionine (SAM) affects placental DNA methylation.

Inverse association between estrogen receptor-α DNA methylation and breast composition in adolescent Chilean girls.

Background: Estrogen receptor-α (ER-α) is a transcriptional regulator, which mediates estrogen-dependent breast development, as well as breast tumorigenesis. The influence of epigenetic regulation of ER-α on adolescent breast composition has not been previously studied and could serve as a marker of pubertal health and susceptibility to breast cancer. We investigated the association between ER-α DNA methylation in leukocytes and breast composition in adolescent Chilean girls enrolled in the Growth and Obesity Cohort Study (GOCS) in Santiago, Chile.

Locus-specific DNA methylation in the placenta is associated with levels of pro-inflammatory proteins in cord blood and they are both independently affected by maternal smoking during pregnancy.

We investigated the impact of maternal smoking during pregnancy on placental DNA methylation and how this may mediate the association between maternal smoking and pro-inflammatory proteins in cord blood. The study population consisted of 27 individuals exposed to maternal smoking throughout pregnancy, 32 individuals exposed during a proportion of the pregnancy, and 61 unexposed individuals. Methylation of 11 regions within 6 genes in placenta tissue was assessed by pyrosequencing.

DNA methylation of candidate genes in peripheral blood from patients with type 2 diabetes or the metabolic syndrome.

Introduction: The prevalence of type 2 diabetes (T2D) and the metabolic syndrome (MetS) is increasing and several studies suggested an involvement of DNA methylation in the development of these metabolic diseases. This study was designed to investigate if differential DNA methylation in blood can function as a biomarker for T2D and/or MetS.

Methods: Pyrosequencing analyses were performed for the candidate genes KCNJ11, PPARγ, PDK4, KCNQ1, SCD1, PDX1, FTO and PEG3 in peripheral blood leukocytes (PBLs) from 25 patients diagnosed with only T2D, 9 patients diagnosed with T2D and MetS and 11 control subjects without any metabolic disorders.

Transgenerational epigenetic inheritance in mammals: how good is the evidence?

Epigenetics plays an important role in orchestrating key biologic processes. Epigenetic marks, including DNA methylation, histones, chromatin structure, and noncoding RNAs, are modified throughout life in response to environmental and behavioral influences. With each new generation, DNA methylation patterns are erased in gametes and reset after fertilization, probably to prevent these epigenetic marks from being transferred from parents to their offspring.

Aberrations in DNA methylation are detectable during remission of acute lymphoblastic leukemia and predict patient outcome.

Aim: Aberrant DNA methylation patterns are a hallmark of cancer, although the extent to which they underlie cancer development is unknown. In this study, we aimed to determine whether acute lymphoblastic leukemia (ALL) patients in clinical remission retained abnormal DNA methylation patters and whether these were associated with patient outcome.

Materials & Methods: We investigated CpG island methylation of genes known to exhibit hypermethylation in leukemia using quantitative pyrosequencing analysis.

Fatty acid chain length and saturation influences PPARα transcriptional activation and repression in HepG2 cells.

Scope: Fatty acids regulate peroxisome proliferator activated receptor α (PPARα) activity, however, most studies evaluated the binding ability of fatty acids to PPARα, which does not necessarily result in PPARα transactivation. We therefore examined dose-response relationships between fatty acids and PPARα transactivation in HepG2 cells. Secretion of apoA-I protein as well as CPT1, ACO, and PPARα mRNA expression, all accepted PPARα targets, were determined as read-outs.

DNA methylation abnormalities at gene promoters are extensive and variable in the elderly and phenocopy cancer cells.

Abnormal patterns of DNA methylation are one of the hallmarks of cancer cells. The process of aging has also been associated with similar, albeit less dramatic, changes in methylation patterns, leading to the hypothesis that age-related changes in DNA methylation may partially underlie the increased risk of cancer in the elderly. Here we studied 377 participants aged 85 yr from the Newcastle 85+ Study to investigate the extent of, and interindividual variation in, age-related changes in DNA methylation at specific CpG islands.

Acquisition of aberrant DNA methylation is associated with frailty in the very old: findings from the Newcastle 85+ Study.

Frailty is a major health problem in older people and, as the population ages, identification of its underlying biological mechanisms will be increasingly important. DNA methylation patterns within genomic DNA change during ageing and alterations in DNA methylation, particularly at gene promoter regions, can lead to altered gene expression. However the importance of altered DNA methylation in frailty is largely unknown.

Do age-related changes in DNA methylation play a role in the development of age-related diseases?

DNA methylation is an important epigenetic mechanism in mammalian cells. It occurs almost exclusively at CpG sites and has a key role in a number of biological processes. It plays an important part in regulating chromatin structure and has been best studied for its role in controlling gene expression.

Epigenetic inactivation of TWIST2 in acute lymphoblastic leukemia modulates proliferation, cell survival and chemosensitivity.

Background: Altered regulation of many transcription factors has been shown to be important in the development of leukemia. TWIST2 modulates the activity of a number of important transcription factors and is known to be a regulator of hematopoietic differentiation. Here, we investigated the significance of epigenetic regulation of TWIST2 in the control of cell growth and survival and in response to cytotoxic agents in acute lymphoblastic leukemia.