Environmental Effects and Epigenetics

The Role of the Environement

Phenotype
(Who we are: size, shapes, blood groups, etc)
/ \
Genotype Environment
(Epigenetics mechanism)

(Combination of genes (Infectious Agents

inherited from parents) toxins, diet, etc.)

Phenotype is determined by genotype + environment

Role for epigenetics (I): Why are identical twins not identical

Role for epigenetics (II): How do organisms generated multiple

phenotypes from the same genotype.
E.x. Haematopoesis

Different Cell-Types Express the Same Proteins

Both a neurones and skeletal muscles have common structural
proteins and enzymes:
 Histones
 RNA polymerase
 Tubulin (structural support)
 Pyruvate kinase

‘housekeeping genes’

Different Cell-Types Express Different Proteins

Neurones:
 Acetylcholinesterase

Skeletal Muscle
 Troponin

‘Differentiation’: The pathway(s) to making cells

Epigenetics depends on mechanisms that regulate gene expression

What is a gene?

Genes are transcriptional units composed of:

1. Structural information coding for a protein
2. Regulatory sequences giving instructions for expression

5’ regulatory sequences controls transcription initiation = gene

PROMOTER

Transcription initiation:
 RNA polymerase cannot recognise transcription start sites
 ‘General transcription factors’ bind and unwind DNA
 Many promoters contain a conserved sequence: the TATA BOX
(~25 bp upstream of start)

Gene Regulations: General Transcription Factors:

 Recognise true gene promoter
 Recruit RNA polymerase II to gene

Transcription initiation
Initiation complex assembly is via stepwise binding of the general
transcription factors
= ‘Basal’ level of transcription

Transcription with gene specific transcription factors

= ‘Activated’ transcription

Gene Regulation
Rates of transcription are controlled by:
 Enhancers (DNA sequences up and downstream of gene)
 Gene-specific transcription (activate and repress)

Transcription Factors and the environment:

 Hormones
 Nutritional signal
 Environmental signal

How DNA is organised – Chromatin structure

The Nucleosome
 Composed of 8 histone
 (H2A, H2B, H3, H4) x2
 Assembles ~200bp DNA

Human Genome
= 3 x 109 bp
= ~2m long

A human (female) karyotype

 2 copies of each chromosome:
o 1 maternal homologue, 1 paternal homologue
o Different versions of the same gene are ‘alleles’ – in a
single coding region
o Human:
 22 pairs of autosomes (1-22)
 2 sex chromosomes (XX or XY)

Example 1: Histone Modification

Histone tails are subject to chemical modification
 Modified by enzyme families
 The environment can influence histone acetylation
If something is so highly conserved, it must be fundamental in the
regulation of gene
 Chemical tags

The ‘Histone Code’

 chromatic
 A layer of information overlaying the DNA
 Involved in turning genes on or off
Nucleosome Modifications
1. Involved in turning genes on or off
2. Respond to changes in environment inside and outside of the
cell

An example of ‘epigenetic regulation’

Example 2: X-inactivation

Females have two X chromosomes, males have one X and a small

gene – poor Y

Dosage Compensation (I)

Sex determination
 Chromosomal difference between sexes
o i.e. Human: XX (female) vs XY (male)
 Dosage compensation equalises gene expression levels

Dosage Compensation (II)

In female mammals (XX)
 1 of 2 Xs is inactivated early in development
 Balances the difference between males and females
Dosage Compensation (III)
 Inactive X chromosomes
 Densely staining ‘Barr body’

Dosage Compensation in Mammals

 X-inactivation is random
 Occurs in the inner cell mass of the blastocyst
 Inactive state is passed on to succeeding cell generations
 X-inactivation is an example of a heritable epigenetic state

Gene Regulation and Epigenetic Mechanisms

 DNA is an inert carrier of information
 Its interpretation (gene expression) defines phenotype
 Environmental effects can impact on gene activity:
o Gene specific transcription factors
o Epigenetic mechanisms (i.e. histone modifying enzymes)
 X inactivation (random)
o Long term chromosome silencing