Epigenetic Regulation Of Gene Expression Flashcards
What is an epigenetic trait?
A stable, mitotically and meiotically heritable phenotype that results from changes in gene expression without alterations in the DNA sequence
What are epigenetics?
The study of the ways in which these changes alter cell- and tissue-specific patterns of gene expression
What is an epigenome?
This refers to the epigenetic state of the cell
Describe epigenetics as mechanisms
Mechanisms that cause chromosome-associated heritable changes to gene expression that are not dependent on changes in DNA sequence
The phenotype off an organism is a product of the interactio; between the genome and epigenome
What mechanisms would epigenetics use?
- Altering the genome without changing the DNA sequence
- The “epigenome” is a specific pattern of modifications to the DNA that is present in the cell at a given time
- Histone modification controls transcription of genes
- Transcription from only one parental allele
Explain how altering the genome without changing the DNA sequence acts as a part of epigenetics
Includes:
- DNA methylation/demethylation
- Histone modification mainly through acetylation/deacetylation called the “Histone Code”
- Action of non-coding RNA molecules
Explain the epigenome being a specific pattern of modifications to the DNA as a mechanism of epigenetics
Over a lifetime:
- DNA remains the same
- Epigenome may change
Explain how Histone modification controls transcription of genes as a mechanism
Histone modification controls transcript of genes
Either:
-Activating or silencing
Explain how transcription from only one parent acts as a mechanism for epigenetics
Two general ways:
- in a very specific way called “Imprinting”
- In a random way called “Monoallelic Epigenetic Expression”
How are epigenetic traits heritable?
Epigenetic states are transmitted through mitosis and meiosis
- Reversible modification of DNA by the addition of removal of methyl groups to cytosine
- Chromatin remodeling the addition or re,oval of chemical groups to histone proteins
- Regulation of gene expression by non coding RNA molecules
What is the methylome?
DNA Methylation: the methylome
The methylome is tissue specific is cell and tissue specific
- Not “fixed” and is reversible
- Can change as cells respond to changing conditions
When does DNA methylation takes place?
DNA methylation in mammals takes place:
- After DNA replication
- During cell differentiation of adult cells
What is DNA methylation?
DNA methylation involves the addition of a methyl group (-CH3) to the 5’ carbon of a cytosine base base to make a 5-methylcytosine
Explain the catalyzation of methylation
Methylation is catalyzed by a family of enzymes called DNA methyl transferases(DNMTs)
DNMT1-maintains methylation pattern through DNA duplication
DNMT2 and 3- create methylation patterns
How does methylation affect the structure of DNA?
- methylation occurs most often on the cytosine adjacent to a guanosine, CpG doublets in DNA on both strands
- Methyl groups occupy the major grove of DNA and prevent the binding of transcription factors
What are CpG islands?
Methylatable CpG-rich regions are not random but are concentrated
Explain how methylation affects transcript
When methylated, the genes are transcriptionally silent
When unmethylated, the genes are available for transcription
About 70% of human genes have a CpG island in their promoter region
How do ,ethylagion patterns differ among tissues?
Methylation pattern is tissue specific and once established , the methylation pattern is maintained for all cells in that tissue through cell division
Methylation patterns of genes are also tissue specific
What purposes does hypomethylation serve?
Hypomethylation of genes in cells generally involved in housekeeping functions such as cell cycle, transcription and RNA processing
Where are the majority of CpG islands located?
Majority of methylated CpG are located in repetitive DNA sequences located in heterochromatic regions of the genome including the centromere
What is the function of heterochromatin methylation?
-Maintains chromosome stability by preventing translocations and other chromosomal abnormalities from occurring
How X chromosomes in females inactivated?
X chromosomes in mammalian females are inactivated by converting them into heterochromatin
What does CpG methylation in euchromatin regions causes?
-Causes a parent specific pattern of gene transcription
What is Chromatin?
Chromatin is composed of DNA wound around an octamer of Histone proteins to form nucleosomes
Contrast loosely packed and densely packed in terms of transcription
Loosely packed DNA allows for RNA polymerase to access the DNA for transcription to occur
Dense packing is transcriptionally silent
What are dense and loose packing influenced by?
Dense and loose packing can be influenced by post-translational modifications to the amino acids near the N-terminal tail of the histone proteins
Give a brief description of Histone modification
Histone modification alter the nucleosomes
- N-terminal tails become modified by acetylation, methylation or phosphorylation
- his changes the way DNA is wrapped around the histones
- DNA methylation is linked to Histone acetylation
How does the Histone tail interact with the DNA phosphate backbone? Why? What effect does this have?
The Histone tails interact tightly with the negatively charged phosphate backbone of DNA -causes transcription to be repressed
Why- The amino tails of Histone proteins, particularly 3 and 4 have many lysine residues
-Lysines are positively charged
What is Histone acetyltransferase(HAT)?
An enzyme which can add an Acetyl group to the lysine residues
How does acetylation affect transcription?
The Acetyl group masks the charge of the lysine residues and the Histone tails no longer bind the DNA
Transcription can occur
How can Acetyl groups be removed?
The Acetyl group can be removed by Histone deacetylase(HDAC)
-Which is guided to regions of DNA that are methylated
Explain HDAC activity when methylation occurs?
If DNA is methylated:
- Histone deacetylase is recruited to the site
- Acetyl group is removed from the Histone tails by HDAC
- Lysine residues becomes positively charged
- The position charge interacts with the negative charge of the DNA badkbone
- “Closed” configuration
What are writers?
Proteins that add chemical groups to DNA and histones
What are readers?
Proteins that interpret these chemical modifications