Epigenetic mechanisms: DNA methylation and histone protein modification

Abstract

Epigenetic Regulation Allows Control of Differential Gene Expression from the Same Genome. Every somatic cell in a given organism contains the same genetic information, which is encoded in a DNA double helix. Yet there are several hundred different cell types in the human body that form four types of tissue and build organ systems that perform vastly diverse physiological functions. This diversity is achieved through developmental programming when differentiation signals and environmental cues converge to regulate temporal and spatial patterns of gene expression in a specific cell type. For example, during neurogenesis, neural progenitor cells acquire their neuronal phenotype by inducing the transcription of neuron-specific genes, whereas cells outside the nervous system maintain nonneural cell fates by permanently suppressing neuronal genes. These different patterns of gene expression in different cells of an organism come about in part through epigenetic mechanisms. Epigenetics is most commonly defined as persistent and heritable changes in gene expression that do not involve modification of DNA. However, in light of recent evidence demonstrating the dynamic nature of epigenetic modifications, especially in postmitotic neural cells, we favor a more mechanistic definition put forward by C. David Allis and colleagues: The sum of the alterations to the chromatin template that collectively establish and propagate different patterns of gene expression and silencing from the same genome (Allis CD, Jenuwein T, Reinberg D (2007) Epigenetics. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY.). According to these authors, chromatin 'signatures' can be viewed as a highly organized system of information storage that can index distinct regions of the genome and accommodate a response to environment signals that dictate gene expression programs. Work done within the past decade has in fact demonstrated that epigenetic mechanisms are utilized by nerve cells to translate early childhood experiences into long-lasting behavioral patterns, store memories, and develop addictive behaviors after exposure to drugs of abuse. In this chapter, we will discuss various molecular events that collectively are referred to as epigenetic regulatory mechanisms and address the importance of these processes in nervous system development and function.