Hiroki Shibuya - Epigenetics Flashcards
What is epigenetics?
The change in gene expression or protein nature that is not dependent on a change in the DNA sequence.
Four types of epigenetics
- Chromatin remodeling
- DNA methylation
- Non-coding RNA-mediated regulation
- Protein conformational change
What is chromatin remodeling?
The use of ATP hydrolysis to alter chromatin architecture by repositioning, assembling, mobilizing and removing nucleosomes.
What is a histone?
A protein. Contains many basic amino acids such as lysine and arginine, which makes them positively charged. They have a long N-terminal which can be modified. They are very well preserved.
The three main histone tail modifications
Acetylation, methylation and phosphorylation.
Effects of histone modifications
Depends on which amino acids that are modified.
Acetylation increases the negative charges on the histones, which weakens the DNA-histone interaction, making the chromtin less condensed.
Methylation can lead to both relaxation and condensation of the chromatin.
Histone coding
Histones are modified, and the specific combination of modifications form a code that signals proteins/enzymes to condense or decondense the chromatin structure. The histone code spreads and forms specific domains on the chromatin.
Heterochromatin, two types
A tightly packed form of DNA. Constitutive heterochromatin and facultative heterochromatin.
Constitutive heterochromatin
All cells of a species package the same regions of DNA in constitutive heterochromatin. In all cells, any genes contained within the constitutive heterochromatin will be poorly expressed. In most organisms, constitutive heterochromatin occurs around the chromosome centromere and near telomeres.
A permanent factor, stable, has a structural function.
Facultative heterochromatin
The regions of DNA packaged in facultative heterochromatin will not be consistent between cell types within a species. The formation of facultative heterochromatin is regulated. Example: the X chromosome in female mammals, one is packaged as facultative heterochromatin and silenced, while the other is expressed.
Not permanent, has genes with potential for expression.
How is methylation inherited in replication?
Since the replication is semi-conservative, the older strands will have a methyl group, which signals that the new strand will also have a methy group at the same position.
Methylation of promoter DNA, effects
A: DNA methylation can prevent the binding of transcription factors and co-factors.
B: DNA methylation can alter nucleosome dynamics.
C: Methylated DNA recruit specific macromolecular complexes that can alter transcription.
DNA methylation linked to histone coding
The histone code signals that methylation of DNA should take place. Methylation of DNA recruits a methyl-DNA-binding protein, which leads to the further condensation of the chromatin.
Non-coding RNA-mediated regulation
Gene regulation can be mediated by short, non-coding RNA, that interfere with RNA by:
- cleavege of target RNA
- translational repression and eventual destruction of target RNA
- formation of heterochromatin on DNA from which target RNA is being transcribed.
Prions
Infectious, misfolded proteins. Can cause mad cow disease if you eat meat from cows that have misfolded proteins. Because prions are not physically linked to chromosomes, their traits are robuslty transmitted to all mitotic and meitoic progeny through cytoplasmic inheritence.
