Integration of genome-wide expression and methylation data: Relevance to aging and Alzheimer's disease

Abstract

The progressive and latent nature of neurodegenerative diseases, such as Alzheimer’s disease (AD) indicates the role of epigenetic modification in disease susceptibility. Previous studies from our lab show that developmental exposure to lead (Pb) perturbs the expression of AD-associated proteins. In order to better understand the role of DNA methylation as an epigenetic modifications mechanism in gene expression regulation, an integrative study of global gene expression and methylation profiles is essential. Given the different formats of gene expression and methylation data, combining these data for integrative analysis can be challenging. In this paper we describe a method to integrate and analyze gene expression and methylation arrays. Methylation array raw data contain the signal intensities of each probe of CpG sites, whereas gene expression data measure the signal intensity values of genes. In order to combine these data, methylation data of CpG sites have to be associated with genes.

Epigenetics: A novel therapeutic approach for the treatment of Alzheimer's disease

“…Developmental exposure to lead (Pb) upregulates genes involved in AD late in life through mechanisms that involves DNA methylation and histone acetylation (Bihaqi et al, 2011; Bihaqi & Zawia, 2012; Wu et al, 2008a). Persistent bidirectional changes in DNA methylation in response to earlier Pb exposure are reported with hypermethylation resulting in a latent reduction in gene expression (Alashwal et al, 2012; Dosunmu et al, 2012). Moreover, cognitive impairment accompanies overexpression of Sp1, BACE1, APP and Aβ late in life following early exposure to Pb and consequential epigenetic alterations (Bihaqi et al, in press).…”

Longitudinal epigenetic drift in mice perinatally exposed to lead

“…These commonly used biomarkers host CpG islands that are variably methylated 19 or differentially methylated, 18,20 respectively, and environmental exposures have been shown to stably influence their epigenetic marks and subsequent gene expression. [21][22][23][24] Therefore, measuring the relative change in DNA methylation from early to adult life in epigenetically labile regions is crucial to determining whether early life Pb exposure can alter the magnitude or direction of epigenetic drift.…”

Infantile exposure to lead and late‐age cognitive decline: Relevance to AD

“…These findings provide evidence that molecular events occurring during critical periods of brain development are reprogrammed by environmental exposure to promote AD-like pathogenesis late in life. Also, we have reported genomewide messenger RNA (mRNA) expression profiling and methylomic analysis that reveal the scope of reprogramming of gene expression in the aging brain as a result of early life exposure and its connection to epigenetic mechanisms acting at the developmental stage [5,6]. …”