Genetics, Epigenetic Mechanism


Article Author:
Nora Al Aboud
Brittany Simpson


Article Editor:
Ishwarlal Jialal


Editors In Chief:
Linda Lindsay


Managing Editors:
Avais Raja
Orawan Chaigasame
Carrie Smith
Abdul Waheed
Khalid Alsayouri
Frank Smeeks
Kristina Soman-Faulkner
Trevor Nezwek
Radia Jamil
Patrick Le
Sobhan Daneshfar
Anoosh Zafar Gondal
Saad Nazir
William Gossman
Pritesh Sheth
Hassam Zulfiqar
Navid Mahabadi
Steve Bhimji
John Shell
Matthew Varacallo
Heba Mahdy
Ahmad Malik
Mark Pellegrini
James Hughes
Beata Beatty
Nazia Sadiq
Hajira Basit
Phillip Hynes
Tehmina Warsi


Updated:
4/5/2019 9:53:51 AM

Introduction

Epigenetics is the study of heritable changes in gene expression that happen without involving any changes to the basic DNA sequence, which ultimately results in a change in the phenotype without a change in the genotype. Epigenetic changes can be influenced by several factors including age, environment, and particular disease state. There are over 100,000 cells in one square centimeter of tissue, and each of these cells contains close to 2 meters of DNA that contain our genetic information. The genetic material in our body is called a genome. DNA is  packaged with proteins known as histones. The DNA and protein complexes are known as chromatin. DNA is wrapped around histone proteins forming repeated units of nucleosome that look like beads on a string. Chromatin is condensed further to form a chromosome. Humans have 46 chromosomes stored in the nucleus. The core of one nucleosome is composed of DNA wrapped around a histone octamer that consists of 2 copies of the major types of histones H2A, H2B, H3, and H4. This organized DNA protein complex allows the cells to regulate what something expresses genes.[1]

Function

Epigenetics forms a layer of control that determines which genes are turned off and which genes are turned on in particular cells in the body. They do this by making chemical modifications of chromosomal DNA and/or structures that change the pattern of gene expression without altering the DNA sequence. Every cell has the same DNA, but every cell has a different function, and the expression patterns of genes are different in each particular cell type. For example, enzyme secreting cells in the intestinal epithelial help break down food. Every cell has its specified function, and that specified function is determined by which genes are on and which genes are off.

All the cells in our body from skin cells, muscle cells, and liver cells contain the same DNA sequence yet; these cells have different structures and functions. This variation and structure in different cells are because only certain genes are expressed within each cell the DNA. Furthermore, the histones can be tagged by tiny chemicals that modify gene expression, these chemical tags cause some genes to be turned on, and some genes turned off. If there were no epigenetic tags, there would be chaos, and the body would not be able to develop a complex interacting system of tissues and organs. For example, muscle cells will have genes turned on that a muscle cell requires and will turn off genes that a liver cell requires; similarly, the liver cell will have genes for muscles turned off and genes that a liver requires turned on. These modifications are known as epigenetic modifications. "Epi" is Greek for "above," therefore, meaning modifications above the genes or on the genes. Epigenetic modification causes lasting changes in gene expression. In a normal human cell, the genetic material is made of the DNA is wrapped around nucleosomes, which are made up of histone proteins. Histone tails come off the histone proteins.

DNA is a combination of 4 nucleotides: G for guanine, C for cytosine, A for adenine and T for thiamin. There are at least 3 different epigenetic mechanisms that have been identified including DNA methylation, histone modification and non-coding RNA (ncRNA)-associated gene silencing. The first one is DNA methylation in which a methyl group is added directly to a cytosine residue that exists in a cytosine-guanine sequence (CpG). For example, many CpG sites make up a CpG island, and the cytosine is methylated. The methylation of CpG sites in promoter regions is associated with gene silencing. DNA methylation turns off genes. The addition of methyl groups is controlled in cells and is carried out by enzymes called DNA methyltransferases.

The second epigenetic modification is histone modification and is usually a post-translational modification of histone proteins. This takes place on the tails of the histone proteins that form that nucleosome. They help form that nucleosome; therefore, each of these histone proteins has a tail that sticks out the side. Each of these tails has various points at which different chemical signals are added making epigenetics complex. There are different chemicals that can be added to the tails resulting in acetylation, methylation,  phosphorylation, ubiquitylation[2],and sumoylation . The position of each of these tags on the tail and whatever is lying next to it greatly influence what these particular chemical tags do; therefore, histone modification is complex, but overall, acetylation opens the DNA allowing for expression. For example, Histone3K9 acetylation correlates with transcription activation, while Histone3k27 trimethylation correlates with transcription repression. Genome-wide patterns of DNA and histone modifications or epigenome are established during early development and are maintained during cell division. In cancer, these patterns are altered and disrupted. Thus, histone modifications are involved in transcriptional activation/inactivation, chromosome packaging, and DNA repair. 

The most recently studied epigenetic mechanism is non-coding RNA-associated gene silencing. A noncoding RNA or ncRNA is a functional RNA molecule that is transcribed from DNA but not translated into proteins. Some of those identified include miRNA, siRNA, piRNA, and lnc RNA. These ncRNAs regulate gene expression or silencing at the transcriptional and post-transcriptional level. Those ncRNAs that appear to be involved in epigenetic processes can be divided into 2 main groups; the short ncRNAs (les than 30 nts) and the long ncRNAs (greater than 200 nts). The 3 major classes of short non-coding RNAs are microRNAs (miRNAs), short interfering RNAs (siRNAs), and piwi-interacting RNAs (piRNAs). Both major groups are shown to play a role in heterochromatin formation, histone modification, DNA methylation targeting, and gene silencing.

Epigenetics is one of the promising future areas of research because it theoretically, it is simpler to turn genes on and off than to change DNA sequence. Some drugs have been approved for human use or are under development to alter the methylation patterns of the DNA or adjust histone modifications. Treatment needs to be selective, targeting the specific cells for which a researcher is looking; otherwise, modifying the wrong genes in specific cells may cause adverse consequences. Epigenetics is a promising and emerging field of medical research which may influence the way people develop and manage disease.

Issues of Concern

As people age, the biggest influences on the epigenome is the environment. Direct influences such as diet can affect one's epigenome. A person who has a healthy diet will have different epigenetic pattern than somebody who has an unhealthy diet. The epigenome can also be influenced by indirect environmental changes, for example, stress.

Clinical Significance

One example of how nutrition influences the epigenome is found in queen and worker bees. These 2 are genetically identical. The only difference is that queen bees are force-fed royal jelly from the larval stage, and the worker bees are fed nectar, pollen, and water. This royal jelly diet switches on genes in the queen. This leads to the queen developing ovaries and a large abdomen for laying eggs. These varied diets switch on particular genes, and the queen develops ovaries while the worker bees remain sterile.

Cancer was the first human disease to be linked to epigenetics. Studies performed by Feinberg and Vogelstein demonstrated that genes of colorectal cancer cells were hypomethylated compared with normal tissues. Also, several mental retardation disorders such as Fragile X, Prader-Willi, and Angelman syndromes are associated with changes in DNA methylation.

Enhancing Healthcare Team Outcomes

The epigenome is changeable; therefore, when things happen, and genes that are inactive must be expressed, they can be altered. This is particularly important during development. The cells are listening for signals to change DNA expression. The signals may come from inside the cell, neighboring cells, or the environment.

Increased understanding of epigenetic mechanisms of disease and gene editing technologies will allow us to understand its role in disease regulation and aid in diagnosis and targeted therapies of many clinical diseases.


Interested in Participating?

We are looking for contributors to author, edit, and peer review our vast library of review articles and multiple choice questions. In as little as 2-3 hours you can make a significant contribution to your specialty. In return for a small amount of your time, you will receive free access to all content and you will be published as an author or editor in eBooks, apps, online CME/CE activities, and an online Learning Management System for students, teachers, and program directors that allows access to review materials in over 500 specialties.

Improve Content - Become an Author or Editor

This is an academic project designed to provide inexpensive peer-reviewed Apps, eBooks, and very soon an online CME/CE system to help students identify weaknesses and improve knowledge. We would like you to consider being an author or editor. Please click here to learn more. Thank you for you for your interest, the StatPearls Publishing Editorial Team.

Genetics, Epigenetic Mechanism - Questions

Take a quiz of the questions on this article.

Take Quiz
Which of the following is true of the term "epigenetic"?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
Which is true of monoallelic expression of a gene?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
Which of the following is not an example of epigenetics?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
DNA packaging is a complex group of reactions involving many proteins that regulate gene expression. Which of the following mechanisms is responsible for the cytogenic changes seen in Fragile X patients?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
Which statement of the following would explain the effect of acetylation of the histones on DNA?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up

Genetics, Epigenetic Mechanism - References

References

Feinberg A, The Key Role of Epigenetics in Human Disease. The New England journal of medicine. 2018 Jul 26     [PubMed]
Allis CD,Jenuwein T, The molecular hallmarks of epigenetic control. Nature reviews. Genetics. 2016 Aug     [PubMed]

Disclaimer

The intent of StatPearls is to provide practice questions and explanations to assist you in identifying and resolving knowledge deficits. These questions and explanations are not intended to be a source of the knowledge base of all of medicine, nor is it intended to be a board or certification review of NP-Genetics. The authors or editors do not warrant the information is complete or accurate. The reader is encouraged to verify each answer and explanation in several references. All drug indications and dosages should be verified before administration.

StatPearls offers the most comprehensive database of free multiple-choice questions with explanations and short review chapters ever developed. This system helps physicians, medical students, dentists, nurses, pharmacists, and allied health professionals identify education deficits and learn new concepts. StatPearls is not a board or certification review system for NP-Genetics, it is a learning system that you can use to help improve your knowledge base of medicine for life-long learning. StatPearls will help you identify your weaknesses so that when you are ready to study for a board or certification exam in NP-Genetics, you will already be prepared.

Our content is updated continuously through a multi-step peer review process that will help you be prepared and review for a thorough knowledge of NP-Genetics. When it is time for the NP-Genetics board and certification exam, you will already be ready. Besides online study quizzes, we also publish our peer-reviewed content in eBooks and mobile Apps. We also offer inexpensive CME/CE, so our content can be used to attain education credits while you study NP-Genetics.