DNA methylation and epigenetic control of cellular differentiation

Abstract

In mammals the genome is shaped by epigenetic regulation to manifest numerous cellular identities. The term epigenetics has been used to refer to changes in gene expression, which are heritable through multiple cell division cycles that are not due to variations in primary DNA sequence. Stable suppression of differentiation genes is required to sustain the undifferentiated state in cells ranging from embryonic stem cells to somatic stem cell progenitors that constantly replenish self-renewing tissues. However, the epigenetic mechanisms behind the maintenance of cellular dedifferentiation are not yet fully understood. Major effectors of epigenetic control include regulators of DNA methylation and histone modification as well as ATP-dependent chromatin remodeling enzymes. These interact with other regulators, such as DNA sequence-specific transcription factors and noncoding RNAs to landscape the genome during development, differentiation and cancer. DNA methylation is a classic and powerful example of the epigenetic inheritance of cellular identity that is widely used in eukaryotes. DNA methylation confers distinct epigenetic states via several mechanisms. Here we discuss fundamental mechanisms of DNA methylation and their interplay with several regulatory pathways that define cellular physiology and differentiation.

Alcohol abuse and cigarette smoking are associated with global DNA hypermethylation: Results from the German Investigation on Neurobiology in Alcoholism (GINA)

“…Neither can it provide data on the molecular mechanisms underlying the effects of alcohol and smoking on global DNA methylation. Also, DNA methylation patterns are frequently tissue-and cell-specific, reflecting tissue-specific regulation of DNA methylation (Khavari, Sen, & Rinn, 2010). Therefore, methylation patterns should ideally be examined in the tissue that is directly related to the outcome of interest.…”

PDGFRβ Expression and Function in Fibroblasts Derived from Pluripotent Cells is Linked to DNA Demethylation

“…The establishment and maintenance of cellular identity following differentiation from pluripotent cell types is dependent on global epigenetic changes that 'landscape the genome' to streamline specific functional programs and maintain a specified cell-lineage fate (Khavari et al, 2010). Differentiation of ESCs and iPSCs towards stable mesenchymal lineages is dependent on changes in DNA methylation of CpG islands that result in characteristic methylation profile that can be used to distinguish specific cells from normal and diseased states (Fernandez et al, 2012).…”

A comparison of DNA methylation specific droplet digital PCR (ddPCR) and real time qPCR with flow cytometry in characterizing human T cells in peripheral blood

“…The DNA methylation status of specific CpG dinucleotides provide markers of cell differentiation in diverse types of mammalian cells, 1 including those of the haematopoietic system. 2,3 Our earlier experiments showed that cell lineage-specific differentially methylated regions (DMRs) distinguish normal human leukocyte subsets and can be used to detect and quantify these subsets in peripheral blood.…”