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Epigenetics
Challenging the traditional dogma of
human health and disease
Epigenetics Definition
• Stably heritable phenotype resulting from
changes in a chromosome without alterations
in the DNA sequence.
• A change in phenotype without a change in
genotype.
• A study of the mechanisms that switch genes
on and off.
https://en.wikipedia.org/wiki/Epigenetics . Accessed
09/19/2016
Epigenome
• Epigenetic mechanisms
operate at the
transcriptional and posttranscriptional level of
gene activity as well as at
the level of protein
translation and posttranslational
modifications.
• Mechanisms include:
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DNA methylation
Histone modifications
ncRNA modifications
Chromatin remodeling
https://www.genome.gov
Epigenetic Modifications
• DNA methylation
– Important regulator of gene transcription
– Methylation occurs at the DNA and histone level
https://www.whatisepigenetics.com
Epigenetic Modifications
• Histone modification
– Covalent post-translational modification to histone
proteins.
– Can impact gene expression by altering chromatin
structure.
– Affects gene expression regulation
https://www.whatisepigenetics.com
https://www.whatisepigenetics.com
Epigenetic Modifications
• Non-coding RNA
– RNA that is not translated into proteins.
– Interacts with mRNA and may prevent protein
translation.
– Regulates gene expression at the transcriptional
and post transcriptional level.
https://www.whatisepigenetics.com
Epigenetic Modifications
• Chromatin Remodeling
– Alterations to histone proteins contribute to the
accessibility and compactness of chromatin.
https://www.whatisepigenetics.com
Epigenetic Associated Diseases
Epigenetic Mechanism
Disease
Aberrant DNA Methylation (hyper and hypomethylation)
Cancer
• Bladder, lymphomas, ovarian, medulloblastoma, colorectal, breast, acute myeloid
leukemia, Barret’s adenocarcinoma, melanoma, gastric, cervical, squamous cell lung.
Autoimmune
• Systemic lupus, erythematosus, subacute cutaneous lupus erythematosus,
scleroderma, inflammatory skin disease.
Imprinting Disorders
• Beckwith-Wiedemann syndrome, Russel-Silver syndrome, transient neonatal
diabetes.
Neurodegenerative Disorders
• Alzheimer’s, Parkinson’s.
Aberrant Histone Modifications
Cancer
• Gastric, colorectal, non-small-cell lung cancer, prostrate, pancreatic, papillary
neoplasm, lung adenocarcinoma.
Autoimmune
• Lupus.
Neurodegenerative Disorders
• Huntington’s disease, schizophrenia.
Cardiovascular Diseases
• COPD
Aberrant miRNA (ncRNA) Expression
Cancer
• Esophageal squamous cell carcinomas, lung, primary head and neck squamous cell
carcinoma, gastric, prostate, melanoma, hepatocellular.
Epigenetic Technologies
• Next-gen sequencing techniques
– DNA methylation
• Bisulfite sequencing (Bi-seq) and reduced –representation Bi-seq
(RRBS).
• Methylated DNA immunoprecipitation sequencing (MeDIP-seq),
methylated DNA capture by affinity purification sequencing (MeCAPseq), and methylated DNA binding domain sequencing (MBD-seq).
• Methylation-sensitive restriction enzyme sequencing (MRE-seq)
– Histone modification
• Chromatin immunoprecipitation followed by sequencing (ChIP-seq)
– Non-coding RNAs
• Detection using RNA-sequencing studies
– Chromatin structure assays
• DNase I hypersensitivity site sequencing (DNase-seq), formaldehydeassisted isolation of regulatory elements followed by sequencing
(FAIRE-seq), sonication of cross-linked chromatin followed by
sequencing (Sono-seq), and chromosome conformation capture
sequencing (3C-seq).
Epigenetic Research in Human Disease
http://learn.genetics.utah.edu/content/epige
netics/twins/
http://learn.genetics.utah.edu/content/epige
netics/twins/
Monozygotic twins Ramon, Romolo,
Joey and David
Agouti twin mice. Digital image.
<http://www.pbs.org/wgbh/nova/body/epige
netic-mice.html>
Epigenetics
“In biology, Darwin and Mendel came to define the
nineteenth century as the era of evolution and genetics.
Watson and Crick defined the twentieth century as the
era of DNA, and the functional understanding of how
genetics and evolution interact. But in the twenty-first
century, it is the new scientific discipline of epigenetics
that is deconstructing so much of what we took as dogma
and rebuilding it in an infinitely more varied, more
complex, and even more beautiful fashion.”
http://www.naturalhistorymag.com/features/142195/beyond-dnaepigenetics/accessed 11/09/2016
References
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https://en.wikipedia.org/wiki/Epigenetics accessed 9/19/2016
http://www.whatisepigenetics.com/what-is-epigenetics/ accessed 09/19/2016
https://www.genome.gov/27532724/epigenomics-fact-sheet/ accessed
09/20/2016
http://learn.genetics.utah.edu/content/epigenetics/intro/ accessed 09/19/2016
Bell, Spector, A twin approach to unraveling epigenetics. Trends in Genetics. 2011
Mar; 27(3); 116-125
http://www.whatisepigenetics.com/fundamentals/ accessed 09/20/2016
Haluskova, J., Epigenetic Studies in Human Diseases. Folia Biologica (Praha) 56, 8396 (2010)
Shuk-Mei Ho, Abbey Johnson, Pheruza Tarapore, Vinothini Janakiram, Xiang Zhang,
and Yuet-Kin Leung. Environmental Epigenetics and Its Implication on Disease Risk
and Health Outcomes. ILARJ. 2012;53(3-4):289-305
http://www.whatisepigenetics.com/dna-methylation/ accessed 9/21/2016
http://www.whatisepigenetics.com/chromatin-remodeling/ accessed 9/23/2016
http://learn.genetics.utah.edu/content/epigenetics/twins/ accessed 09/26/2016
http://www.naturalhistorymag.com/features/142195/beyond-dnaepigenetics/accessed 11/09/2016