1.08 Epigenetics Flashcards
Describe the Epigenetic mechanism in Agouti Mice.
The offspring of a parent fed a methyl donor rich diet will have more brown offspring than yellow mice. Methylation of the agouti gene causes the agouti mRNA to not be produced, leading to brown mice (yellow is normal). However, the yellow and brown mice are genetically identical.
Describe the Epigenetic mechanism in Queen Bee genetics
All female bees are genetically identical. Queens get fed ‘royal jelly’, a protein rich substance.
Royal jelly silences a gene, which encodes for an enzyme that silences a group of queen gene.
What is Histone?
Histone is a highly alkaline protein found in eukaryotic cell nuclei that package and order DNA
What is the Nucleosome?
The basic unit of DNA packaging in eukaryotes, consisting of a segment of DNA wound in sequence around eight histone protein cores
What is chromatin?
Chromatin is the combination or complex of DNA and proteins that make up the contents of the nucleus and the cell
What is Epigenetics?
It represents the science for studying heritable changes of DNA, not involving changes in DNA sequence, that regulate gene expression.
Chromatin structure and dynamics is a key factor in gene expression. What four mechanisms effect these?
Substitution of core histones with variant histones ATP-Dependent chromatin remodelling Post-translational modification of histone tails DNA modifications (DNA methylation)
Describe how histone variants alter gene expression.
Histones are proteins. Histones are conserved in most cells.
Histone variants can alter the structure and function of chromatin when they substitute core histones
Describe how Post-Translational Histone Modification can effect gene expression
Like all proteins, histone can undergo modifications altering their normal function.
These modifications include: acetylation, methylation, ubiquination, phosphorylation.
These later the net charge of histones and alter inter-nucleosomal interactions.
Provide a platform for chromatin-binding proteins that alter chromatin compaction.
Modifications can have differing effects on gene activity, e.g. Monomethylation of H3L27 will lead to activation of the gene while di-methylation of the same histone will lead to repression.
Describe how ATP-Dependent Chromatin Remodelling can alter gene expression
Remodelling of nucleosomes by using ATP allows accessibility for proteins of transcription to parts of the gene (promotor, introns/exons etc.) that were previously blocked by the nucleosome
Describe how DNA modifications such as DNA methylation effect gene expression
DNA methylation is the process whereby a methyl group is added to the cytosine or adenine DNA nucleotides. This modification typically silences the gene and halts transcription.
Bind to regions called CpG islands
What are CpG islands?
They are C-G repeat sequences in the DNA. Known as gene ‘Hot Spots’ and have a high susceptibility to methylation. Typically located in the 5’ region of genes (upstream from the promoter) and are involved in the bind ing of activator proteins to the enhancer region.
Describe 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 descendent cells. X-inactivation is controlled by epigenetic mechanisms such as DNA methylation and histone modifications. Chromosome becomes ultra compacts, so much so, that no information can get out.
What is Genomic Imprinting?
It is a phenomenon in which the phenotype of the offspring depends on the source of the chromosome containing the imprinted gene.
For the vast majority of autosomal genes, expression occurs from both alleles simultaneously.
A small proportion of genes are imprinted.
Describe Prader-Willi Syndrome
A deletion at chromosome 15.
A developmental and growth disorder: Hypotonia, hyperphagia, obesity, hypogonadism, mild intellectual disability
Relevant gene: SNRPN
