TRILLO (BS BIO 2018) 04/15/2019

BIO 30 GENETICS
[008] EPIGENETICS
8.1 DEFINITION OF EPIGENETICS
8.2 EPIGENETIC MECHANISMS
8.3 ENVIRONMENTAL FACTORS & EPIGENOMES
8.4 NUTRIGENOMICS

[8.1] DEFINITION OF EPIGENETICS

Epigenetics – the study of mechanisms that change gene expression by modifying the DNA without modifying
its base sequence.
Epigenetics – study of changes in regulation of gene activity.

Epigenome – genome-wide distribution of epigenetic marks which sit on top of the genome that tell which genes
to switch on or off.

Wolf Reik (Cambridge University) Epigenetic Mechanisms control accessibility of the genome at
“Development is epigenetic.” the right time and place.

[8.2] EPIGENETIC MECHANISMS

1. DNA METHYLATION

 Methyl is added in the cytosine of 5’ – CG-3’ dinucleotides

 Methylation accounts for the very specific patterns of silencing and activating genes in every cell.
 Active genes are low in methyl groups (under methylated).
 (in mammals) Methylation regulates DNA structure and gene expression from the earliest zygotic stages.

Brown & Yellow Twin Laboratory Mice

 Both mice possess the agouti gene ----------------------------------- agouti gene
Variable methylation region
 Genetically identical but phenotypically different
 Agouti gene produces a protein that regulates a number of other genes.

BROWN MOUSE YELLOW MOUSE

----------------------------------- agouti gene
METHYLATED NOT METHYLATED

 Mouse 1 is fed with methyl-rich foods  Mouse 2 is fed until obese

 Methyl group binds to the agouti gene that  Develops diabetes and tumors
silences it during development  Agouti gene is unmethylated thus actively expressing

TRILLO (BS BIO 2018) 04/15/2019

TRILLO (BS BIO 2018) 04/15/2019

2. MODIFICATION OF HISTONES

 Histone methylation – tightens up DNA thus restricting access to genes.

 Histone acetylation – unravels the DNA making more available to activation.
Histone acetylation – reduces net positive charge of histones and weaken binding with DNA
Histone acetylation – facilitates binding of transcriptional factors to nucleosomal DNA

CORE HISTONES: H2A, H2B, H3, H4

 Histone Fold Domain – is involved in interactions with other histones and wrapping DNA around the
Histone fold domain – nucleosome core.
 Amino Terminal Tail Domain – extends outside the nucleosome.
Amino Terminal Tail Domain – Lysine in ATTD can be modified by acetylation

3. NON-CODING RNA

 Andew Z. Fire & Craig C. Mello (Nobel Prize 2006) – discovery of RNA interference (RNAi)
 RNA interference (RNAi) – is a biological process in which RNA molecules inhibit gene expression or
translation, by neutralizing targeted mRNA molecules.
 Short RNA’s (21 – 25 nucleotides long) – small interfering RNAs.

RNA INTERFERENCE PATHWAY

1. (Dicer) regonizes double stranded RNA – dsRNA

2. Dicer cuts dsRNA into single stranded RNA – siRNA
3. RNA-Induced Silencing Complex (RISC) binds to double stranded siRNAs and unwides them into single
stranded siRNA
4. RISC uses the small dsRNAs to repress gene expressions by destroying homologous mRNA transcribed
from the target DNA.

[8.3] ENVIRONMENTAL FACTORS AND EPIGENOMES

 Environmental factors:
1. Diabetes
2. Stress
3. Prenatal nlutrition

 Folate – strong methyl donor; prevent neural tube defects during pregnancy

 Epigenetic drug – silence bad genes and turning on good ones.

Epigenetic drug – can turn on tumor suppressing genes and battle cancer cells

 Autistic individuals show methylation that results to reduced expression of the oxytocin receptor gene.

TRILLO (BS BIO 2018) 04/15/2019

TRILLO (BS BIO 2018) 04/15/2019

[8.4] ENVIRONMENTAL FACTORS AND EPIGENOMES

Nutrigenomics – (nutritional genomics) study how food affect our genes

Nutrigenomics – how genetic differences can affect the way we respond to nutrients
Nutrigenomics – study of molecular relationships between nutrition and responds of genes

5 TENETS OF NUTRIGENOMICS

1. Diet can be a risk factor for a number of diseases.

2. Gene expression and structure of the human genome can be altered directly or indirectly by the chemicals
in our diet.

3. The degree to which diet influences the balance between healthy and disease stages may depend on the
genetic make-up of an individual.

4. Some diet-regulated genes are likely to play a role in the onset, incidence, progression and severity of chronic
diseases.

5. Dietary intervention based on knowledge of nutritional requirement, nutritional status and genotype can be
used to prevent, mitigate or cure chronic diseases.

BIOACTIVE FOOD COMPONENTS

Tea Polyphenols

Soybeans Genistein

Plants Isothiocyanates

TRILLO (BS BIO 2018) 04/15/2019