Epigenetics Flashcards
(35 cards)
Epigenetics
the inheritance of gene “states” (or potential for genes to be expressed) through mitosis predominantly
Biochemical mechanisms of epigenetic gene regulation (3)
- DNA methylation 2. histone covalent modification 3. Chromative remodeling complexes
genetics
inheritance of genes through alleles that determine a given phenotype (allele is inherited in a predictable way)
Why is epigenetics important for medicine?
Modifications are reversible so they can be targeted for drug therapy
How are epigenetic changes inherited?
through mechanisms that influence chromatin structure
euchromatin
regions of chromatin that are less condensed
heterochromatin
regions of chromatin that are highly condensed
constitutive heterochromatin
regions of chromatin that are always highly condensed
facultative heterochromatin
euchromatic regions that can assume a more condensed chromatin organization
Mechanism of DNA methylation
DNA methyltransferases covalently attach a methyl group to the # 5 carbon of cytosine in CpG dinucleotides
How is DNA methylation heritable?
DNA methyltransferase 1(DNMT1) copies methylation marks with the DNA replication complex onto the new daughter strand based on methylation of the parent strand (place for mistakes to happen/differences in gene expression)
How can DNA methylation be reversed?
group of enzymes (TET1, TET2, TET3) convert methyl group to -OH and then make to normal (H)
Mechanisms for reversing CpG methylation patterns in the genome (2)
- passive loss via global/regional inhibition of DNMT1 during replication (slow) 2. Active demethylation by TET enzymes (fast)
CpG island
region of DNA that have CpG associated with regulatory genes (important site for inheritance)
What is the general effect of DNA methylation on DNA?
generally correlates with condensed chromatin and transcriptional repression
How does DNA methylation directly affect gene transcription?
methyl groups on cytosines prevent DNA-binding proteins from interacting with their binding sites on chromatin
How does DNA methylation indirectly affect gene transcription?
methyl-cytosine binding proteins can recruit protein complexes that act to repress transcription and reduce expression of the gene
How can histones be modified? (4 major ones)
- Acetylation 2. methylation 3. phosphorylation 4. ubiquination ON TAILS OF HISTONES
Mecahnism of the direct effect of Histone Acetyl Transferases (HATs)
HAT adds acetyl group to lysine which changes its +1 charge to a neutral charge which changes DNA structure (less condensed)
General effects of histone acetylation on chromatin organization and gene transcription
- acetylation correlates with less condensed chromatin and active gene transcription 2. histone deacetylation correlates with condensed chromatin and transcriptional repression
What is the indirect effect of HATs?
acetyl-lysine is recognized by proteins called histone code readers and recruit proteins that influence transcription
What is the mechanism of histone methylation?
Histone methyltransferases (HMTs) covalently attach a methyl group to lysine or arginine side chains (can add 1, 2, or 3 methyl groups).
What is the difference between the lasting effects of acetylation and methylation?
methylation is more stable
How is histone methylation reversed?
Histone demethylases can reverse the effect of HMTs