Epigenetics-Beyond the Genome in Alcoholism

By Starkman, Bela G.; Sakharkar, Amul J. et al. | Alcohol Research: Current Reviews, Fall 2012 | Go to article overview

Epigenetics-Beyond the Genome in Alcoholism


Starkman, Bela G., Sakharkar, Amul J., Pandey, Subhash C., Alcohol Research: Current Reviews


Alcohol is one of the most widely used addictive drugs, and continued use and abuse can lead to the development of tolerance and dependence (Koob 2003a; Tabakoff et al. 1986). Numerous studies have shown that both genetic and environmental risk factors play a role in the development of alcoholism (Ducci and Goldman 2008; Edenberg and Foroud 2006; Farris et al. 2010). Genetic studies in both humans and animal models of alcoholism (Contet et al. 2011; Crabbe et al. 2006; Pignataro et al. 2009; Spanagel et al. 2010; Tabakoff et al. 2009) have identified several genes that may be critical in the pathophysiology of alcoholism (see figure 1). Recently, researchers have identified mechanisms that result in heritable changes in gene expression but are caused by other processes than changes in the underlying DNA sequence (i.e., epigenetic mechanisms) as a promising area of research to better understand the molecular mechanisms of human diseases, including psychiatric and alcohol use disorders (AUDs) (Moonat et al. 2010; Tsankova et al. 2007). This article reviews some of the epigenetic mechanisms that seem to play a role in the development of AUDs.

What Is Epigenetics?

The genome encompasses the complete set of genetic material (i.e., DNA) that determines the development of an organism and all its traits and characteristics (i.e., the phenotype). Changes (i.e., mutations) in the DNA can lead to the development of various diseases, including AUDs. In comparison, the epigenome, as first defined by Waddington (1942), refers to chemical modifications that occur within a genome without changing the DNA sequence (Holliday 2006; Murrell et al. 2005; Waddington 1942). Epigenetic alterations include the direct addition of methyl groups to (i.e., methylation of) DNA and the chemical modification of the proteins around which the DNA is wrapped (i.e., histone proteins) to form the chromosomes. Both of these mechanisms work in concert to remodel the structure of the protein-DNA complex (i.e., the chromatin) and regulate gene expression (1) (Kornberg 1974; Olins and Olins 1974; Hsieh and Gage 2005).

Chromatin is made up of units called nucleosomes, which consist of approximately 147 base pairs of DNA wrapped around a complex of eight histone proteins that comprise the histone core (figure 2) (Jenuwine and Allis 2001; Smith 1991). This core structure, which also is referred to as the histone fold domain, consists of a central heterotetramer of histones H3 and H4 and two heterodimers (2) of histones H2A and H2B (Luger et al. 1997; Smith 1991). The histone proteins assemble at one end called the carboxy (C) terminal to form the histone core, with the other end, in the amino (A)-terminal "tail" region, projecting out from the histone core (figure 2). This N-terminal region is made up mainly of the amino acids lysine and arginine (Hsieh and Gage 2005; Mersfelder and Parthun 2006). The majority of epigenetic histone modifications occur at the N-terminal tail of the histones and include methylation as well as addition of acetyl groups (i.e., acetylation), phosphate groups (i.e., phosphorylation), binding of a small molecule called ubiquitin (i.e., ubiquitylation), or addition of a molecule called ADP ribose (i.e., ADP-ribosylation) (Jenuwine and Allis 2001; Smith 1991). The most recognized and well established of these epigenetic modifications include histone acetylation and histone and DNA methylation, which control the accessibility of chromatin to essential transcriptional proteins mediating the first step in the conversion of the genetic information encoded in the DNA into mRNA (i.e., transcription), which then serves as template for the synthesis of protein products in a process called translation. By controlling DNA accessibility, these epigenetic modifications play a crucial role in the regulation of gene transcription (Abel and Zukin 2008; Feng and Fan 2009).

Another epigenetic regulatory mechanism involves microRNAs (miRNAs), a class of noncoding RNAs approximately 21 to 23 building blocks (i. …

The rest of this article is only available to active members of Questia

Sign up now for a free, 1-day trial and receive full access to:

  • Questia's entire collection
  • Automatic bibliography creation
  • More helpful research tools like notes, citations, and highlights
  • Ad-free environment

Already a member? Log in now.

Notes for this article

Add a new note
If you are trying to select text to create highlights or citations, remember that you must now click or tap on the first word, and then click or tap on the last word.
One moment ...
Default project is now your active project.
Project items

Items saved from this article

This article has been saved
Highlights (0)
Some of your highlights are legacy items.

Highlights saved before July 30, 2012 will not be displayed on their respective source pages.

You can easily re-create the highlights by opening the book page or article, selecting the text, and clicking “Highlight.”

Citations (0)
Some of your citations are legacy items.

Any citation created before July 30, 2012 will labeled as a “Cited page.” New citations will be saved as cited passages, pages or articles.

We also added the ability to view new citations from your projects or the book or article where you created them.

Notes (0)
Bookmarks (0)

You have no saved items from this article

Project items include:
  • Saved book/article
  • Highlights
  • Quotes/citations
  • Notes
  • Bookmarks
Notes
Cite this article

Cited article

Style
Citations are available only to our active members.
Sign up now to cite pages or passages in MLA, APA and Chicago citation styles.

(Einhorn, 1992, p. 25)

(Einhorn 25)

1

1. Lois J. Einhorn, Abraham Lincoln, the Orator: Penetrating the Lincoln Legend (Westport, CT: Greenwood Press, 1992), 25, http://www.questia.com/read/27419298.

Cited article

Epigenetics-Beyond the Genome in Alcoholism
Settings

Settings

Typeface
Text size Smaller Larger Reset View mode
Search within

Search within this article

Look up

Look up a word

  • Dictionary
  • Thesaurus
Please submit a word or phrase above.
Print this page

Print this page

Why can't I print more than one page at a time?

Full screen

matching results for page

Cited passage

Style
Citations are available only to our active members.
Sign up now to cite pages or passages in MLA, APA and Chicago citation styles.

"Portraying himself as an honest, ordinary person helped Lincoln identify with his audiences." (Einhorn, 1992, p. 25).

"Portraying himself as an honest, ordinary person helped Lincoln identify with his audiences." (Einhorn 25)

"Portraying himself as an honest, ordinary person helped Lincoln identify with his audiences."1

1. Lois J. Einhorn, Abraham Lincoln, the Orator: Penetrating the Lincoln Legend (Westport, CT: Greenwood Press, 1992), 25, http://www.questia.com/read/27419298.

Cited passage

Welcome to the new Questia Reader

The Questia Reader has been updated to provide you with an even better online reading experience.  It is now 100% Responsive, which means you can read our books and articles on any sized device you wish.  All of your favorite tools like notes, highlights, and citations are still here, but the way you select text has been updated to be easier to use, especially on touchscreen devices.  Here's how:

1. Click or tap the first word you want to select.
2. Click or tap the last word you want to select.

OK, got it!

Thanks for trying Questia!

Please continue trying out our research tools, but please note, full functionality is available only to our active members.

Your work will be lost once you leave this Web page.

For full access in an ad-free environment, sign up now for a FREE, 1-day trial.

Already a member? Log in now.