A Beginner’s guide to the

construction and maintenance

of a human

➢DNA Structure

➢How DNA makes proteins,

the building blocks of life

➢EPIGENETICS –

how it changes how DNA works

➢WHY do we have epigenetics?

➢Where is it all going? 1

DNA

➢HELIX

➢Basepairs, A +T, c + g

➢Twists and knots

➢Codons, amino acids

and proteins

2

DNA REPLICATION

2b

ADENINE

CYTOSINE

GUANINE

THYMINE

2c

ADENINE

Cytosine

Guanine

Thymine/uracil

Alanine

Arginine

Asparagnine

Aspartic acid

Cysteine

Glutamic acid

Glutamine

Glycine

Histidine

Isoleucine

Leucine

Lysine

Methionine

Phenylalanine

Proline

serine

Threocine

Tryptophan

Tyrosine

valine

AAA

AAC

aag

|

|

|

|

|

|

|

vttc

Ttg

ttt

250,000

To

1,000,000

proteins

4DNA Codes

64CODONS

20Amino acids

Histone proteins

Amino AcidsHistone Tail

( H2A H2B H3 H4 x 2 in EACH Histone)8 Histones in an OCTOMER

DNA 147 Basepairs create a Neucleosome

Histone Octomer

2d

How does dna manufacture proteins?

➢m rna

➢ nc rna

➢mi rna and small rna

3

Chromosomes

➢23 pairs

➢22 pairs plus an odd couple

➢Genes can count

➢Females are complicated

3a

3e

Have we cracked the genome?

➢20 to 24k (2%) code for protein

➢What do the hundreds of thousands do?

4

4a

EPIGENTICS?

How do we know it exists?

Is epigenetics why we don’t

grow teeth in our eyeballs?

5

TV Twins : Adam and Neil pearson

5a

AGOUTI MICE

5b

Proof steps for epigenetics

➢Prove every cell has complete dna

toads, eggs…. Big, easy, quick,

huge numbers, see through

➢Cloning – resetting a cell to zero

➢How does the body do it?

What IS epigenetics?

6

What does it do?

“increase or decrease the creation

of proteins from the script dna &

script notes through rna.”

Simples!7

How does an egg and a sperm

become a human?

➢Resetting - but not complete.

➢Fight between male and female genes

➢Man not so good at it.

8

Increasing specialisation as

a cascade of epigenetic

effects trigger more.

9

STEP 1 : A Blastocyst is created

STEP 2 :OCT 4TriggersCell Differentiation.

Cell differentiation startsand cascades like falling Dominoes.

pluripotent

totipotent

Waddington’s landscape

6b

9a

normal

9b

Metamorphosis in insects – the

ultimate in epigenetics?

9c

The mechanisms of

epigenetics

➢Methylation

➢Acetylisation

(Histone modification)

10

Methylation 1

➢Addition of a methyl group to DNA

➢Molecular weight of a base pair is 600 Da (daltons)

➢Methyl group is 15 Da. 2.5% increase.

Grape on a tennis ball.

➢Cytosine, c c is the only one of the dna bases that gets

methylated.

➢Cytosine becomes 5-methylcytosine 5 is the position, not a

value.

➢Caused by enzymes DNMT1, DNMT 3A, oe BNMT 3B

➢ usually only A C followed by a G becomes methylated,

called a CpG

➢Higher the methylation the less effect on the

transcription into rna

➢CpG concentrates in dnA into islands found upstream

of genes in promoter regions. Promoter regions are

at the start of dna to rna coding sections.

Methylation Protein ProductionBut not always!

Attracts other turn off proteins

11

Methylation

(some carbon atoms not shown, for clarity)12

Early proof of methylation

12a

acetylisation

➢Specialised histone modification

for short lived changes to turn protein

coping genes on (But not always.)

➢Marks lysine

13

Acetylisation modification

➢At least 100 histone readers identified

➢Plastic, unlike methylation change in response to

environmental stimuli – like alcohol consumption

drug addiction, insulin.

➢Allows rapid testing of non genetic responses MUCH

quicker than evolution.

➢If effective can be transferred into histone

methylation.

14

15

16

Afghanistan stability model

16a

Turning off/up/down a gene

➢Permanent

➢Persistent

➢transitory

Neurons >

methylation

Skin

(histone packing)

Liver alcoholic

breakdown,

Histone packing

17

Copying cpg methylation

EG - SKIN

17b

WHY?

➢Faster than dna copy errors

➢More responsible for evolution

➢Lamarck has the last laugh.

18

18b

Epigenetic effects

1. Short term

2. Long term

3. generational

19

1. Short term

➢Alcohol in liver

➢Adrenaline

➢Oestrogen

➢Insulin

And so on…….19a

2. Long term

➢Agouti mouse colour

➢skin

19b

3. generational

➢Dutch hunger winter

➢Swedish study of male weight

➢foetal alcohol syndrome

➢chemicals

20a

20b

Rett syndrome

➢Dna methylation

➢M & cp2 mutation

➢Effects can be reversed in mice

21

KABUKI syndrome

➢Mutation in gene mll2

➢Mll2 protein is an epigenetic writer

- adds methyl groups to lysine

in position 4 on histone h3

23

PHF 8 eraser malfunction

➢Phf8 removes methylation from

lysine at position 20 on histone H3

➢Similar effects to kabuki but one

adds and the other fails to delete

methylation.

24

Angelman & prader-willi

The body KNOWSWhich parent the

Chromosome cameFrom.

ANGELMAN PRADER-WILLI 25

current

➢Cancer medication- cloaking removal- replication suppression

➢Alzheimer’s tau protein suppression.

➢issues

22

Future

➢Medecine:-

problems

ethics

23

Epigentics and mental health

24