Epigenetic Mechanisms

Question 1

DNA Methylation

Answer 1

For transcription to take place, proteins need to bind to the promoter region of genes in DNA - not possible if there are methyl groups already present.
Methylation of the Cytosine leads to gene silencing. Methyl groups are dded to Cytosine by methyl transferase enzymes.
This process typically happens during cell differentiation (switching off of genes by methylation, e.g. if producing a liver cell, non-useful genes are methylated)

‘Maintenance methyltransferase’ copies pre-existing methylation patterns onto the new DNA strand during DNA replication (ie mitosis) – so liver cells reproduce more liver cells, not hair-growing or skin cells.
In other words, daughter cells do not lose information of their function and the environment.

It was thought that you cant inherit the methylation changes that happened to you parents, they are erased - BUT it was found that some become re-established! Though not all by any long shot.
‘Remethylation’ occurs at implantation

Question 2

Histone Modification & Chromatin Remodelling

Answer 2

Normally, bits of DNA become freed from heterchromatin ‘spool’ to be accessed by transferase for translation

• N-terminal tails of histones need to be loosened to make heterochromatin losen to euchromatin
• Histone tails undergo post-translational modifications that alter their interaction with DNA and nuclear proteins. In particular, tails of histones H3 and H4 can be covalently modified at several residues.
• Modifications influence several biological processes including gene expression, DNA repair and chromosome condensation
• Dynamic and unpredictable mechanism, we know less about it
• There is horizontal transfer of this kind, we don’t know much about vertical transfer but it seems likely

Question 3

Alternative Splicing

Answer 3

• Removal of introns and reconnection of exons in multiple ways that will be translated into multiple protein isoforms… hence one gene can produce multiple proteins
• Major regulatory process which supplements transcriptional control
• There are several possibilities for alternative splicing, key experimenter of new proteins
• Not known how more successful proteins produced are then replicated, or how less useful ones are abandoned

Question 4

MicroRNA

Answer 4

• microRNA has 22 base pairs – tiny
• Can fine-tune gene expression during development and differentiation
• Targets specific areas of mRNA which have sequence complementarity
• Leads to post-transcription gene silencing through translational repression, but might influence histone and DNA modification
• Could lead to cures for cancers, by stopping translation of gene products that cause cancer
• We don’t know much, lots of potential, expensive to research

Question 5

Definition of Epigenetics

Answer 5

1. The interaction among genes and between genes and environment that lead to a given development and bring the phenotype alive (Waddington 1942)
2. Mechanisms of inheritance that do not include the DNA sequence (Nanney 1958)

Question 6

Human Genome Project

Answer 6

Human genome project found that we have just the same number of coding genes as a plant, around 25,000, not many for such a complex animal
- Problem describing individual phenotype using genes alone, as there is not a 1:1 ratio of genes to proteins
- You cannot read the genetic code and make an organism
- You can have the same genes as another, but differences in transcribing, splicing and translation can change your gene expression and phenotype.
- ‘Slijpers goat’, born with no forelimbs, radical body changes over lifetime as a result of upright posture: developmental plasticity (rounder pelvis, more pibedal-like legs)
• But no genetic mechanism that gives rise to this… phenotypic plasticity.