3. Epigenetics Flashcards
Epigenetics
The study of heritable mechanisms that affect the transcriptional state of a gene which cannot be explained by DNA sequence
3 human DNA methyltransferases
DNMT1, DNMT3A, DNMT3B
Consequences of DNA methylation (5)
- Hypo: Genome instability
- Hyper: Promoter silencing
- Deamination: meCpG->TpG mutation
- UV: Inc. UV-induces mutations
- Carcinogen: Carcinogen-induced mutations
Transcriptional epigenetic mechanisms
- DNA methylation + chromatin remodelling
- X chromosome inactivation + genomic imprinting
- Cancer
- Position effect
Chromatin remodeling
1) Covalent histone modifications by specific enzymes, e.g., histone acetyltransferases (HATs), deacetylases, methyltransferases, and kinases
2) ATP-dependent chromatin remodeling complexes which either move, eject or restructure nucleosomes.
Post-transcriptional epigenetic mechanisms
RNAi, miR, lncRNA
RNAi
RNA interference
- Gene inactivation, both of specific genes and perhaps endogenous viruses, transposons, retroviruses
miR
MicroRNA
- 20-23 nucleotide long RNAs interacting with the 3´UTR region of target mRNAs and via this mechanism blocking their translation
LncRNA
Long non-coding RNAs
- Mechanism of action based on molecular interaction with nucleic acids and protein
X chromosome inactivation: Will both X be equally silenced in each tissue?
No. Different distribution of X in different tissues
What is XIST?
- X-inactive specific transcript
- Non-coding RNA
- Stable expression only from inactive X
- Required to initiate silencing
Genomic imprinting
The non-equivalent expression of genes based on parent-of-origin
Causes of Prader-Willi syndrome
- Paternal deletion of 15q11-13 (70%)
- Maternal UPD (28%)
- Wrong imprinting (<2%)
Causes of Angelman syndrome
- Maternal deletion of 15q11-13 (70%)
- Wrong imprinting (8%)
- UBE3A mutation (around 8%)
- Paternal UPD (4%)
Abnormal imprinting of growth promoting/silencing genes leads to
Cancer
