Epigenetics Flashcards
What is epigenetics?
The phenomenon where genetically identical cells can express their genome differently, because of either cytosine methylation of DNA or histone modifications. This can cause phenotypic differences.
What are the two main ways of epigenetic modifications in eukaryotes?
Histone modifications
Cytosine methylation of DNA
What is heterochromatin?
Densely packed chromatin, less accessible.
What is euchromatin?
Less densely packed chromatin, more accessible.
What is the purpose of Polycomb proteins (Pc-G)?
The function of the polycomb group proteins is mainly to maintain epigenetic gene silencing across cell divisions. They don’t initiate repression, but they can maintain it.
What is position-effect variegation?
When gene regions that are normally in euchromatin are packed into heterochromatin and silenced - this can occur in a stochastic pattern, and the silencing may vary from cell to cell.
How does histone modification work?
The histone proteins consist of octamer protein complexes that the DNA is wrapped around. The amino terminus tails of the histone can be modified in different ways, for example by methylation or acetylation. The histone code determines however the modifications affect the accessibility of the DNA.
What is a commonly modified amino acid at the amino tails of the histone proteins?
K - Lysine
In the histone machinery: what are writers, erasers and readers?
Writers: proteins that establish the mark on the histones.
Erasers: proteins that remove the marks on the histones.
What are writers and erasers that add and remove acetyl groups from histones called, respectively?
Writers: histone acetyltransferases (HATs)
Erasers: histone deacetylases (HDACs)
What are writers and erasers that add and remove methyl groups from histones called, respectively?
Writers: histone methyltransferases (HMTs)
Erasers: histone demethylaces (HDMs)
What happens when lysine residues are acetylated?
The positive charge of histones are reduced, therefore weakening their interaction with the negatively charged phosphate DNA backbone. Opens the configuration.
What happens when residues are methylated?
Methylation adds neutral charge and increases histone interaction
Give some examples of heterochromatin histone codes.
H3K9me2, H3K9me3, H3K27me1-3
What is HP1 and what is its function?
HP1 is a protein that binds to methylated histones in mammals and self-aggregates, creating a higher order chromatin structures.
What is H3K4me associated with?
Actively transcribed genes.
What is H3K9me associated with?
Less transcribed genes.
What is CENH3?
A variant of histone H3 that accumulates at the centromere and is necessary for centromere maintenance.
What are chromatin remodelers?
Proteins that use ATP to remove histones from the chromatin and incorporate other variants in its place. This is another layer of regulation.
What is DNA methylation?
Methylation of cytosine residues in DNA and works as a type of transcriptional repressor. It is reversible and is performed by methyltransferases.
What are CpG islands?
In mammals, methylation occurs at cytosine residues located adjacent to guanine residues. CpG islands are regions of the genome have a high abundance of CpG. CpG islands are often found in transposons, repetitive regions and promoters - places where DNA may need to be inaccessible.
About how many active genes have CpG islands on their promoters?
60-70%
What is the purpose of the Dmt1 enzyme?
Sites in the genome that are fully methylated (methylated on both strands) will be hemimethylated after replicated. Dnmt1 recognizes these sites and recruits methyltransferases to fully methylate the daughter strands.
How is bisulfite treatment of DNA used to determine sites of cytosine methylation?
The DNA is sequenced and saved as a reference. Treating the DNA with bisulfite will convert all unmethylated cytosines to uracil, which means they will be read as thymines by the replication fork and Adenine is incorporated into the complementary strand. Methylated Cs are resistant to the treatment. When the DNA is sequenced again, it will be possible to pinpoint the unmethylated sites by comparing it to the reference.
What is genomic imprinting?
An epigenetic phenomenon that determines the expression of genes depending on they are maternally or paternally inherited.
How is X-chromosome inactivation connected to epigenetics and explain what Barr bodies are related to this?
X-chromosome inactivation occurs in organisms (usually females) with two X-chromosomes, where one X per somatic cell is inactivated by histone methylation. This produces a Barr body - i.e one Barr body per somatic cell. Also called X-chromatin. This is a form of dosage compensation.
How does the dosage compensation (inactivation of one X) mechanism work?
A gene called Xic is located around the centromere. From this, large amounts of a ncRNA called Xist is transcribed, and Xist coats the whole chromosome, inhibiting transcription. Xist also attracts histone modifications, resulting in heterochromatin formation and inactivation of the X.
What are some key biological processes that DNA methylation plays an important role in?
Silencing of transposons
Regulating the silencing and accessibility of promoters
Genomic imprinting
X-chromosome inactivation
Suppression of repetitive element transcription
