0527 - Epigenetics - AK Flashcards
What is the definition of Epigenetics?
Epigenetics describes heritable changes of DNA that do not involve changes in the DNA Sequence.
At what level does Epigenetic Regulation occur?
Epigenetic regulation occurs at the DNA (transcriptional level).
What are the two forms of information in the genome?
Genetic Information provides the building block for the manufacture of all proteins needed for the cell functional activity. Epigenetic Information provides additional instructions on how, when and where this information should be used.
How does the structure of DNA relate to its relative expression?
When DNA is in a naked duplex (unwound), it is more accessible and more likely to be expressed. When DNA is compressed, it is less like those genes will be accessible to be expressed.
What are the Four Mechanisms that control Chromatin structure and Dynamics?
- Substitution of Core Histones with Variant Histones2. ATP-Dependent Chromatin Remodeling3. Post-Translational Modification of Histone Tails4. DNA Modifications (e.g. Methylation)
What is the mechanism of ATP-dependent Chromatin re-modeling?
When Nucleosomes bind to regulatory sequences, such as enhancers, repressors and promoters, they impede the process of DNA transcription. ATP-dependent Chromatin remodeling involves the mechanical displacement of Nucleosomes from these key sites to allow Transcription Factor binding that will influence transcription.
What is the mechanism of Post-Transcriptional Histone-Modification?
Post-translational Histone Modifications can alter the net charge of Histones, alter Inter-Nucleosomal interactions or provide a platform for Chromatin-binding proteins that alter Chromatin compaction. The types of modification are important as they can either promote or inhibit subsequent gene transcription; these include Methylation, Acetylation, De-acetylation and Ubiquitination.
What is the mechanism of DNA methylation?
DNA Methylation is a biochemical process whereby a Methyl group is added to the Cytosine or Adenine DNA Nucleotides via strong covalent bond. DNA Methylation usually results in gene silencing to halt transcription.
Where do Methyl groups bind?
Methyl groups bind to regions called CpG Islands (are 1000-2000bp in length) and contain multiple CpG sites, which describe a phosphate in between Cytosine and Guanine Nucleotides. CpG islands are known as ‘hot spots’ due to their susceptibility to Methylation and are located in the 5’ region of genes. Methyl groups most commonly bind to Cytosine, but can also bind to Adenosine.
What are the differences in Chromatin between High Gene Expression and Low Gene Expression?
When a Gene is switched on the Chromatin is in an open or active conformation, the Cytosines are unmethylated, the Histones are Acetylated, which allows unhindered binding of Transcription Factors to enhancers/suppressors/promoters. When a Gene is switched off, the Chromatin is in a condensed or silent conformation, the Cytosines are most likely Methylated and the Histones are De-acetylated.
What is X-Inactivation?
One of the Two X-chromosomes in every cell in a female is randomly inactivated early in Embryonic development with fixed inactivation in all subsequent descendant cells. This inactivation is achieved via DNA Methylation and Histone modifications. The Active form of an X-chromosome is denoted as Xa, and an inactivated X-chromosome is denoted as Xi and is known as a Bar Body. Once an X-Chromosome has been inactivated, subsequent divisions of that cell will also have the same genomic code in an active formation.
What is Genomic Imprinting?
Genomic Imprinting is a phenomenon in which the phenotype of the off-spring depends on the source of the Chromosome containing the imprinted gene, i.e. whether the trait expressed has genotypic roots in either the Maternal or Paternal DNA.
