Biotech Articles
Publish Your Research Online
Get Recognition - International Audience

Request for an Author Account   |   Login   |   Submit Article
 
 
HOME FAQ TOP AUTHORS FORUMS PUBLISH ARTICLE
 
 

Mechanism of Epigenetics

BY: Sandhya Anand | Category: DNA | Submitted: 2011-03-19 22:30:27
       No Photo
Article Summary: "Epigenetics is the occurrence of changes in gene expression independent of the DNA sequence. There are different mechanisms through which the process occur and are used as research tools. The article describes the processes involved in epigenetics..."


Share with Facebook Share with Linkedin Share with Twitter Share with Pinterest Email this article
     


Epigenetics refers to all mitotically and meiotically heritable changes in gene expression which are not coded in the DNA sequence. They are not decided by the changes in DNA. The study focuses on the changes in gene regulation and gene expression which are independent of the genomic sequence. Epigenetic gene activities become stable and can be inherited through the generations very rarely. There is no change in the primary DNA sequence.

Epigenetic studies are done on singe genes or gene sets. When these studies are expanded to include the changes of the entire genome, it is referred to as epigenomics.

Epigenetics acts mainly through four different mechanisms.


1. DNA Methylation
2. Chromatin remodelling
3. Histone modification
4. RNA interference/interactions

1. Modification at the DNA level

These modifications are cancelled during the process of gametogenesis and embryogenesis. Thus it is an epigenetic phenomenon but not inherited over the generations.
a. Cytosine methylation
It is the addition of methyl group to the Cytosine base of the DNA sequence to form 5' methyl Cytosine (Thymine). Any mutation at 5' methyl cytosine site in the DNA sequence converts it into Uracil and therefore hard to be identified and repaired.

b. Methylation at promoter site
When the methylation occurs at the promoter site, the transcription process gets suppressed.

Methylation is important for

• Silencing transcription
• Genomic imprinting
• X chromosome inactivation
• Protecting the genome from transposition
• Tissue specific gene expression and regulation
• Heterochromatin
• Developmental controls
• Cancer therapy

Defects in the methylation cause diseases such as Systemic lupus erythematosus (SLE), Immunodeficiency, and facial anomalies (ICF) syndrome. Demethylation of promoter sequences increases chemosensitivity, adhesion, response to interferons, and immunogenicity while it helps to decrease growth of cancerous cells.

2. Chromatin remodeling

Chromatin remodeling includes the shifting of nucleosome cores. The process is known as nucleosome sliding. The shift results from disassembling and reassembling the units of nucleosome core. The process is one of the major factors controlling the gene expression by induction and repression.

The remodeling is brought about by SWI/SNF family of ATPase complexes. There are four types of complexes based on the type of ATPases. These are SWI2/SNF2, imitation switch (ISWI); INO80; and Mi-2 (CHD1).


3. Histone modification

There are a lot of histone modifications which are typically conserved over evolutionary processes. These include
• methylation of lysine and arginine residues
• acetylaton of lysine
• phosphorylation of serine and threonine residues
• proline isomerization
• monoubiquitylation
• sumoylation

These modifications can occur in both coding as well as non coding sequences of genome. Some modifications are specific to either active or inactive regions of transcription. These are influenced by the developmental stage, phase in cell cycle, stress, and other environmental factors.

a. Histone acetylation

Acetylated histones are found to open the chromatin and thus enable transcription. The acetylation of Histones are carried out by histone acetylases. These enzymes form part of chromatin remodeling and transcription complexes. The N-terminal Lysine residues undergo acetylation and this causes the Histone proteins to lose their positive charges. The affinity between DNA and histones gets reduces and the promoter regions become easily accessible to the enzymes initiating transcription.

When histones are deacetylated, they are less aceessible to transcription and are tightly packed. The deacetylation of histones is carried out by the enzyme HDAC or histone deacylase.
b. Histone methylation
c. Histone phosphorylation
Phosphorylation of Histones occurs during mitosis, signal transduction pathways like the ERK pathway.

d. Histone ubiquitilation
Ubiquitilation of histones has been found to cause heritable gene silencing and inactivatin of X chromosome.

4. RNA interference.

Epigenetic regulation is influenced by the presence of non protein coding RNAs. These RNAs form an essential part in RNA interference. The resultant small double stranded RNA molecules inhibit gene expression by interacting with the nascent RNA molecule, DNA sequence, or by other mechanisms involving chromatin modifiers. These siRNA molecules are involved in the formation of RISCs (RNA induced Silencing Complexes). The complexes thus formed promote epigenetic silencing by cleavage of RNA molecule or through RNA directed DNA methylation. The process of translation gets inhibited temporarily but doesn't eliminate the gene expression.

The above mentioned process may be specific even to the type of cell and the resultant epigenome is susceptible to changes induced by external stimuli or environmental factors. Any abnormalities in regulation of epigenesis can result in diseases including cancer. Global hypomethylation has been found to alter the chromatin structure resulting in oncogene activation. Hypermethylation and silencing the tumor suppressor genes has also been found in many cancerous cells. The research tool has been used widely in drug designing for cancers.

About Author / Additional Info:


Search this site & forums
Share this article with friends:



Share with Facebook Share with Linkedin Share with Twitter Share with Pinterest Email this article

More Social Bookmarks (Digg etc..)


Comments on this article: (0 comments so far)

Comment By Comment

Leave a Comment   |   Article Views: 25966



Additional Articles:

•   Use of Biofactories as Renewable and Sustainable Resources

•   Antisense Technology - A Breakthrough Research

•   Virtual Screening- a Promising Approach to Drug Discovery

•   Celiac Disease: New Advancements in Detection and Therapy




Latest Articles in "DNA" category:
•   Identifying a Specific Clone in CDNA and Genomic Library

•   Biotechnolgical Techniques For DNA Analysis

•   DNA Extraction:Procedure and Importance in Forensics

•   Chromosomal Aberrations and its Types

•   Gene Knockout in Mice

•   DNA Repair Types: Excision, Postreplication, Recombination and Lesion Removal

•   Microarrays and Gene Expressions - Principle and Procedure

•   Human Cytogenetics - Karyotype

•   Experimental Issues in Microarrays

•   Nuclear pre-mRna Splicing: The Story of Introns and Exons

•   Chain Termination Method: A Generic Method For DNA Sequencing

•   Transposable Elements - The Story of Jumping Genes

•   RNA Interference - The Art of Gene Silencing

•   Protein Biosynthesis: Decoding the Code (Part-1)

•   Protein Biosynthesis: Decoding the Code (Part - 2)

•   Mutagenesis - Types and Uses

•   C-Value, An Unsolved Paradox?

•   Techniques of Epigenetic Studies

•   DNA Binding Motifs - Part 1



Important Disclaimer: All articles on this website are for general information only and is not a professional or experts advice. We do not own any responsibility for correctness or authenticity of the information presented in this article, or any loss or injury resulting from it. We do not endorse these articles, we are neither affiliated with the authors of these articles nor responsible for their content. Please see our disclaimer section for complete terms.
Page copy protected against web site content infringement by Copyscape
Copyright © 2010 biotecharticles.com - Do not copy articles from this website.

ARTICLE CATEGORIES :
Agriculture Bioinformatics Applications Biotech Products Biotech Research
Biology Careers College/Edu DNA Environmental Biotech
Genetics Healthcare Industry News Issues Nanotechnology
Others Stem Cells Press Release Toxicology  


  |   Disclaimer/Privacy/TOS   |   Submission Guidelines   |   Contact Us