STBP2022: Gene expression

Epigenetic regulation

Jasper James PhD

Jabatan Sains Biologi & Bioteknologi

FST UKM
Outline
Epigenetic regulation
• DNA methylation
• Histone modifications
• Chromatin remodeling
Epigenetic
Heritable changes Reversible

Gene expression or cellular phenotype

Without DNA sequence alteration

Epigenetics Development E.g. Nerve vs muscle cell

Same DNA, different function
changes
Age E.g. newborn vs adult vs elderly
Level of DNA methylation decreases with age
Epigenetic & health
Infections
Pathogens can change your epigenetics
e.g. M. tuberculosis changes histones – turns off IL-12B

Nutrition during pregnancy

Healthy vs unhealthy food affects epigenetics
e.g. abnormal levels of methylation in children developed during
famine
Chromatin Remodeling
A dynamic process that involves alteration in
the structure and accessibility of chromatin,
thereby influencing gene expression.

Involves histone modifications

• Acetylation
• Methylation
which alters the interaction between
histones and DNA and affect chromatin
compaction.
Histone acetylation & deacetylation (activation)
Acetylating and deacetylating enzymes act on core histones. Histone
acetyl transferases (HATs) are part of multiprotein complexes
recruited to chromatin when activators bind DNA.

• HATs acetylate lysines in the amino-terminus of core histones.

• The negative charges of acetyl groups decrease the positive
charges of the histones, reducing their affinity for DNA.
• Acetylation of histones changes 30-nm chromatin to 10-nm
fiber, making promoter more accessible for transcription.
• The effect is reversible. When histone deacetylases (HDACs)
remove acetyl groups, 30-nm chromatin reforms.

Histone acetylation neutralizes positive charge of histone, more

relaxed chromatin structure and increased accessibility of DNA
for transcription.
 Chromatin Remodeling – during transcription

30 nm fibre

10 nm fibre

Chromatin and DNA Helix Form Chromosomes: Nucleosomes slide apart during
chromatin remodeling, increasing transcription factors' access to a gene and thereby
activating it. The DNA will then make mRNA, the blueprint for protein production.
Histone methylation (silencing)
Methylation is catalyzed by histone methyltransferase.
Histone demethylase reverses methylation.

DNA methylation can result in gene silencing by inducing a

compacted chromatin that that restrict transcription factor
access to DNA.
 DNA methylation
CpG island (or CG island)
• a CpG site, i.e., the 5'—C—phosphate—G—3’
• Length > 200 bp
• GC% > 50%
• Present in ~70% human promoters

Methylation of CpG island cause silencing effect

Tools to study epigenetics Epigenomic study

• Whole genome bisulfite sequencing

(WGBS): to study DNA methylation
patterns at the single-nucleotide level.
DNA is treated with sodium bisulfite,
which deaminates unmethylated
cytosines, converting them to uracils,
while methylated cytosines remain
unchanged.

• Chromatin immunoprecipitation
sequencing (ChIP-seq): to study
protein-DNA interactions, particularly
interactions involving histone
modifications or transcription factors.
Immunoprecipitated DNA fragments
are sequenced, providing a genome-
wide map of protein-binding sites.

etc.
Epigenomic profiling
There’s more to it..
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Tutorial
THANK YOU!