Epigenetic mechanisms

1. Epigenetic Mechanisms
By
Peyman Ghoraishizadeh
Department of Obstetric& Gynecology
Universiti Putra Malaysia

2. Definition of Epigenetics
• Changes in gene expression or phenotype that don’t involve changes
to the DNA sequence (1)
• Its defined as heritable changes in gene activity and expression that
occur without alteration in DNA sequence (2)

3. Mechanism of Epigenetics
• Mechanisms
Chromatin Remodelling & Histone Modification
DNA Methylation
Non-coding RNA mediated pathway
Prion
Epigenetic code:
Consist of Both DNA methylation and histone modifications
Defining code in every eukaryotic cells
Genetic code in each cell is the same
Epigenetic code is tissue and cell specific (3)

4. Chromatin structure
• Chromatin= DNA+ Protein
• Basic unit of chromatin is nucleosome
• Chromatin structure is dynamic

5. Euchromatin&Heterochromatin
Heterochromatin controls chromosomal
Stability and prevention of
Mutations and translocations
Heterochromatin cause genomic
Imprinting and
X chromosomal inactivation

6. Nucleosome
• nucleosome contains
147 bp of genomic
DNA wrapped around
an octamer of
histone Proteins
approximately 1.75
times

7. Chromatin remodeling
• Chromatin remodeling is accomplished through
two main mechanisms:
• Post trans translational modification of the amino acids
that make up histone protein
• Addition of methyl group to DNA

8. Histone Modifications
• Post-translational modifications:
• – Acetylation – Lys
• – Methylation – Lys and Arg
• – Phosphorylation – Ser and Thr
• – Ubiquitination – Lys

9. Histone Acetylation&Deacetylation
• Histone acetylation
• – Histone acetyl transferases (HATs)
• Adds acetyl groups to histone tails
• Reduces positive charge and weakens interaction of histones with DNA
• Facilitates transcription by making DNA more accessible to RNA
polymerase II
• Histone deacetylation
• – Histone deacetylases (HDACs)
• Removes acetyl groups from histone tails
• Increases interaction of DNA and histones
• Represses transcription (usually)

10. Histone Acetylation&Deacetylation
• Acetylation has two functions:
reduce the positive charge on the lysine residues
Destabilise interactions between histone tails
and structural proteins

11. Histone Methylation
• Histone methylation
• Histone methyl transferases (HMTs)
– Histone lysine methyl transferases(HKMTs)
.Methylate lys (k) residues
. Protein argenin methyl transferase (PRMTs)
.Methylate arge(R) residues
Methylation can result in activation or repression
Of expression
trimethylation of histone H3 at lysine 4 (H3K4) is an active mark for transcription
dimethylation of histone H3 at lysine 9 (H3K9), a signal for transcriptional silencing (4)

12. • Small Ubiquitin-like Modifier (or SUMO) proteins
• Ubiquitin
• ADP-ribosylation

13. DNA Methylation
• Involves the addition of a methyl group to DNA
• Usually to the number 5 carbon of the cytosine
• pyrimidine ring
• Effect: reducing gene expression
• Catalyzed by DNA methyltransferases (DNMTs)
• Predominantly found found in CpG sites of mammalian genome
Silencing:
• Methylation of CpG sites within the promoters of genes can lead to their
silencing, a feature found in a number of human cancers (eg. silencing of tumor
• suppressor genes)
Activation:
• In contrast, the hypomethylation of CpG
sites has been associated with the over-expression of oncogenes within cancer cells.

14. Epigenetic and gene regulation

15. References
• 1.http://en.wikipedia.org/wiki/Epigenetics
• 2.Bird A.Nature ,447 ,396-98[2007]
• 3. Turner B (2007). "Defining an epigenetic code". Nat Cell Biol 9 (1): 2–6.
• 4.Gupta, Swati; Se Y. Kim, Sonja Artis, David L. Molfese, Armin Schumacher, J. David Sweatt, Richard E. Paylor, and Farah D. Lubin (10 March 2010). "Histone Methylation Regulates
Memory Formation". The Journal of Neuroscience 30 (10): 3589–3599