The document discusses epigenetics and epigenomics, focusing on mechanisms like DNA methylation and histone modifications that regulate gene expression without altering the DNA sequence. It highlights the role of non-coding RNAs, chromatin remodeling, and the impact of environmental factors on epigenetic regulation, as well as the significance of these processes in development, diseases, and aging. Additionally, it emphasizes the potential for therapeutic applications in treating epigenetic-related disorders.

1. Epigenetics & Epigenomics
Dr. Shiny C Thomas, Department of Biosciences, ADBU

2. The Norrbotten epigenetics story
• http://io9.gizmodo.com/how-an-1836-
famine-altered-the-genes-of-children-born-d-
1200001177

3. Epigenetics
• Epigenetics studies stably heritable traits that
cannot be explained by changes in DNA
sequence.
• Functionally relevant changes to the genome that
do not involve a change in the nucleotide
sequence.

4. Epigenetics- Mechanisms
• Covalent modifications in chromatin
• DNA- DNA methylation (CpG); hydroxymethylation
• Histone - lysine acetylation, lysine and arginine
methylation, serine and threonine phosphorylation, and
lysine ubiquitination and sumoylation
• Modified histones as post translational modification
• DNA methylation – 5mC the 5th base, methyl
transferases; genetic imprinting

5. Epigenetics- Mechanisms
• Histone modifications – N terminii (histone tails) are
most susceptible to modifications
• Eg. Acetylation of the K14 and K9 lysines of the tail of histone
H3 by histone acetyltransferase enzymes (HATs) is generally
related to transcriptional competence/induction. Reason-
positively charged amine group changes to neutral amide
linkage. This removes the positive charge, thus loosening the
DNA from the histone = transcription induction
• Histone lysine methyltransferase (KMT) and
demethyltransferase (KDM) modulate epigenetic
effects

6. Epigenetics- Mechanisms
• DNA methylation of repeats, transposons
• Environmental factors- Methyltransferases
• RNA
• Alternative splicing
• Non coding RNA – MicroRNA (MiRNA)
• About 60% of human protein coding genes are regulated by
miRNAs
• 50% of miRNA genes are associated with CpG islands

7. Functions
• Development
• Transgenerational inheritence

8. Epigenome
• Epigenomics is the study of the complete set
of epigenetic modifications on the genetic
material of a cell, known as the epigenome.
• Most characterised: DNA methylation and
Histone modiciations

9. Methods
• Histone modification assays:
• ChIP-Chip; ChIP Seq (array hybridization, NGS)
• DNA methylation assays:
• Restriction endonuclease based
• Compare by use of methylation sensitive
enzyme vs insensitive enzyme
• Restriction Landmark Genome Scanning (RLGS),
array hybridisation, NGS (latest)

10. Human epigenome project
http://www.epigenome.org/index.php?page=p
roject

11. Regulatory and Epigenetic
landscapes of mammalian genes

12. • Mechanisms of gene regulation that can be stably
inherited through mitosis and (sometimes)
meiosis, but can be established and released
without changing the DNA .
• The study of heritable changes in gene activity
that are not caused by changes in the DNA
sequence.
• It includes all forms of gene regulation
WHAT IS EPIGENETICS

13. • All our cells contain the same genes, different
cells and tissues differ in which genes they
express.
• These differences are created and maintained by
gene regulation, not by changes in the DNA
sequence.
• Some gene regulation has evolved to respond
easily to changing conditions within the lifetime
of a single cell.
Functions of Epigenetic Regulation

14. 1. DNA methylation
2. Covalent Histone modifications
3. Chromatin remodelling or non covalent
modifications
4. Non coding RNA
Epigenetic Mechanisms

15. • It plays an important role in regulating gene
expression.
• Methylation of DNA is direct chemical
modification of a cytosine nucleotides within a
continuous stretch of DNA, specifically at the 5-
position of the pyrimidine ring.
• Not all cytosines can be methylated; cytosines
must be immediately followed by a guanine in
order to be methylated.
DNA Methylation

16. • Histones are highly basic proteins whose function is to
organize DNA within the nucleus.
• Histone modifications can lead to either activation or
repression depending upon which residues are modified and
the type of modifications present. For example, lysine
methylation leads to transcriptional activation.
• These modifications serve as epigenetic tags or marks.
• Histone proteins have tails that can have a number of post-
translational modifications including acetylation,
methylation, phosphorylation, ubiquitylation, sumoylation,
ADP-ribosylation, glycosylation etc.
Covalent Histone Modification

17. • It is the post translational modification of the
amino acids that make up histone proteins
• As the histones increase the compaction of the
DNA , it depresses the genetic activity and vice–
a-versa.
• TYPES OF CHROMATIN REMODELLING
1.Sliding over 2. Histone eviction
3. Replacement with variant histones
Chromatin Remodelling / Non
Covalent Modification

19. • It includes short interfering RNAs (siRNAs), microRNAs
(miRNAs), and long non coding RNAs (lncRNAs) .
• It play important roles in gene expression regulation at
post-transcriptional level by mRNA degradation, during
splicing.
miRNAs
• A micro RNA is a small non-coding RNA molecule.
• It is about 22 nucleotides long.
• It functions in RNA silencing and post-transcriptional
regulation of gene expression.
Non coding RNA

20. siRNA
• Short interfering RNA or silencing RNA.
• double-stranded RNA molecules, 20-25 base pairs
long.
• Role in the RNA interference (RNAi) pathway.
lncRNAs
• Long non-coding RNAs (long ncRNAs, lncRNA)
• longer than 200 nucleotides.
• LincRNA play an important role in developmental
processes such as X-chromosome inactivation and
genomic imprinting.

21. • RNA interference
RNA interference (RNAi) is a mechanism whereby the expression
of genes is disrupted through the action of double-stranded RNA
molecules.
• X inactivation (Lyonization)
Females silence one of their two X-chromosomes through a
process referred to as X-chromosome inactivation, to compensate
gene dosage disparities.
• Genomic imprinting
Phenomenon by which certain genes are expressed in a parent of-
origin- specific manner. If the allele inherited from the father is
imprinted, it is thereby silenced, only the allele from the mother is
expressed and vice versa.
Specific Epigenetic Regulation

22. • The maintenance of the epigenetic state is important
throughout life for the production of differentiated cells from
adult stem cells and proper gene expression in specific cell
types.
• The epigenomic state is dynamic and tightly regulated, and
misregulation of epigenetic patterns are observed in many
human diseases and multiple types of cancers.
• Changes in the epigenome are also correlated with the aging
process.
• Some diseases have epigenetic causes like Prader-Willi
syndrome, Angelman syndrome are all the result of
uniparental disomy (UPD), a condition in which a person
inherits both homologous chromosomes from the same
parent. UPD can be the result of gene deletion, translocation,
or a defect in imprinting.
EPIGENETICS IN DEVELOPMENT &
DISEASE

23. • They are the means to maintain and manipulate the large
amount of data produced by sequencing epigenomes.
• Epigenetic marks are associated with specific diseases, tools
can be developed to diagnose patients and measure the
severity of disease.
• In therapeutic epigenetics several drugs, such as DNA
methyltransferase inhibitors and histone deacetylase
inhibitors, are already used in cancer treatment.
• Likewise, better understanding of the various epigenetic
diseases and syndromes may lead to effective drugs designed
to overcome epigenetic defects.
CONCLUSION