Epigenetics Flashcards
What is epigenetics?
Gene regulation system: for tissue-specific expression- turning genes on & off due to factors (e.g. environment, diet/nutrition)
Types of modifications on histones?
- Methylation
- Acetylation
- Phosphorylation
- Ubiquitination
Significance of epigenetics
Relevant to the study of:
- Somatic cell therapy
- cloning & transgenic therapy
- Cancer
- Viral taency
- Developmental abnormalities
How variable expression can be useful in our knowledge in other fields eg cancer?
To understand what stimulates certain genes to be expressed and how it is silenced or enhanced.
Where can the modifications take place that affect gene expression?
DNA (C) and Histone tails
Histone methylation: including the amino acids are marked, # of methyl groups added, and the enzymes involved in methylation and demethylation.
- Lysine & Arganine on histone tail methylated (1-3x methyl group per lysine on tail)
- Added by: Histone Methyltransferase
- Removed by: Lysine-specific demethylase I
What affect does methylation on histone have on chromatin structure, and why? How does this affect expression?
More methylation (hypermethylation) = more condensed chromatin = Heterochromatin = less active bc DNA binding molecules (DBP) can’t access DNA = genes not/less expressed
Histone acetylation: including which amino acid are marked, # of acetyl group added, and the enzymes involved in acetylation and deacteylation.
- Lysines on histone tail acetylated (1x acyl per Lys group & not methylated)
- Added by: Histone acyl transferase
- Removed by: Histone de-acetylase
What affect does acetylation have on chromatin structure? How does this affect expression?
More acetyl (Hyperacetylation) = less condensed chromatin = Euchromatin = more active bc DBP can access DNA = genes expressed
DNA methylation: the CpG site, the enzymes involved in initiation, and in maintenance of methylation.
- CpG: The C (that has a G next to it on the same strand) is methylated
- Initiated by De Novo (make new) DNA methyl transferase > used for adding new methyl groups on DNA
- Maintained by Maintanance methyl transferase > used on a dividing cell that has replicated & match methylation pattern from parent- allele was inherited from
What affect does DNA methylation have on gene expression (transcription)?
Methylation prevents BINDING of DBP on REGULATORY region (not coding region) ≠ transcribe
Effects of DNA methylation on regulatory regions and on up-regulation & down-regulation genes.
Methylation inactivates REGULATORY region => incr. or decr. expression
- Switch off up-reg. gene = decr. expression
- Switch off down-reg. gene (e.g silencer) = incr. (/enhanced) expression
How the marks are reprogrammed via DNA replication?
- DNA replication => new strand from old strand
- Maintenance transferase recognise hemi-methylated DNA (methyl on old strand but not on new) and adds methyl group on new strand on C (w/ CpG) => both strands methylated
What happens in gametogensis? in terms of methyl groups
- De-methylation in early development of primordial germ cells
- Re-methylation occurs (males earlier)
- Re-methylation completed prior to meiosis
What happens in embryogenesis? in terms of methyl groups
- De-methylation after fertilisation (paternal genome quicker rate bc has enzyme)
- Re-methylated @ implantation
a) What is imprinting? b) How does imprinting affect allele expression? c) How are the marks reset?
a) genes that are expressed depending on whether it was inherited from mum or dad (Mono-allelic expression)
b) Only one gene (from mum or dad) is active (the other is silenced)
c) Both alleles of offspring re-set to match methylation pattern from the allele which was inherited from the one parent (de/methylated)
What is dosage compensation in mammals?
Inactivate 1X chromosome in females (compensate for the only X in males) by converting it into heterochromatin in early embryo development (1000 cell stage)
Explain how dosage compensation in mammals is achieved.
- 1X chromosome randomly selected to be inactivated = Barr body
- A region on X chromo. Xic (X inactivation centre) = codes for RNA (Xist)
- Xist coats chromo
- => transcriptional gene silencing & chromatin left condensed = remain inactivated
What happens in phosphorylation?
Serine AA phosphorylated
- Added by: Kinases
- Removed by: Phosphatases
What happens in Ubiquitination?
Ubiquitin (protein) added to side chain of Lysine
- Added by: Ubiquitin conjugating enzyme
- can’t be removed bc end point command»_space; recognised as trash/ useless
What is bromodomain?
effector molecule that targets acetyl groups > regulates gene expression by winding or unwinding chromatin
Give an example of X-inactivation
tortoiseshell coloured cat
- occurs in females (XX) & males (XXY)
- red allele on 1 X chromo. & black allele on another X chromo.
- random patches of red & black occur bc of random inactivation of X in early development
What happens when Drosophila “white” gene is near heterochromatin region (instead of being more upstream)?
expression of gene stops = red w/ patches of white in eyes of fly (called variegation)
How does methylation protect DNA?
heterochromatin/ tightly wound DNA can’t be accessed by endonucleases
