Concepts of Genetics: Unit 4
DNA methyltransferase
Methylation occurs via enzyme DNA methyltransferase, which attaches to 5 position of cytosine base.
Factors promoting Epigentic Changes
- Genomic imprinting - X-chromosome inactivation - Cell Differentiation * Temperature * Diet * Toxins
Transversion mutation
- Mutation changing a purine into a pyrimidine or a pyrimidine into a purine (A->C; T->G)
Intragenic supressor
A mutation at a second site that relieves the effect of the first mutation and restores the original phenotype (psuedo reverant) on the same gene
Silent mutation
A mutation that changes a single nucleotide, but does not change the amino acid created.
Using coat color in mice and the development if female honeybees as examples, how can dietary factors cause epigenetic modifications and thereby lead to phenotypic effects?
Happens mostly in the early stages of development. Dietary may affect level of DNA methylation. Effects S-adenisylmethionine or function of DNA methyltransferase and thereby influence particular genes are methylated or not.
Localization of histone variants effect on Epigenetic Gene Regulation
Histone variants may become localized to specific location (near promoter) and affect transcription
Depurination
Loss of a purine base (A or G)
Let's suppose that a vertebrae organism carries a mutation that causes cells that normally differentiate into nerve cells to differentiate into muscle cells. A molecular analysis of this mutation revelaed that it was a gene that encodes a methyltransferase. Explain how an alteration in methylationtranferase could produce this phenotype.
Methylation may be responsible for methylating and inhibiting a gene that causes cell to become a muscle cell. Methyltransferase is inactivated by the mutation.
Supressor mutation
Mutation at a locus that returns the allele to the original phenotype with a different mutation
Germline mutation
Mutation that occurs directly in sperm or egg cell or precursor cell that produces gametes
Chromatin Remodeling effect on Epigenetic Gene Regulation
Nucleosomes moved or evicted. When near promoter, level of transcription is altered
Deamination
The removal of an amino group from an amino acid. (C to U or T)
Deleterious mutation
describes mutations that are harmful to an organism
Histone Variant
histone genes that have accumulate mutations that change the amino acid sequence
Up promoter mutation
increases affinity for regulatory factors, increases rate of transcription
Frameshift mutation
mutation that shifts the "reading" frame of the genetic message by inserting or deleting a nucleotide Addition/deletion in DNA
Transition mutation
- Mutation changing one purine into another purine or one pyrimidine into another pyrimidine (A->G;T->C)
Molecular mechanisms that underlie epigenetic gene regulation
1) DNA Methylation 2) Chromatin remodeling 3) Covalent histone modification 4) Localization of histone variants 5) Feedback loop
Two effects of insulator
1. Barrier to changes in chromatin structure (gene within insulator is unaffected) 2. Blocking effect of enhancers (Gene A effected, but insulator keeps it from effecting Gene B)
Nonsense mutation
A mutation that changes an amino acid codon to one of the three stop codons, resulting in a shorter and usually nonfunctional protein.
Neutral mutation
A mutation that has no effect on the organism
Missense mutation
A point mutation in which a codon that specifies an amino acid is mutated into a codon that specifies a different amino acid.
Base substitution mutation
A type of mutation involving replacement or substitution of a single nucleotide base with another in DNA or RNA molecule.
Briefly describe 3 ways that ATP-dependent chromatin remodeling complexes may change chromatin structure.
ATP-dependent chromatin remodeling may effect position of nucleosomes, evict histones, and may replace histones with histone variants.
Feedback loop
Activation of gene that encodes transcription factor may result in feedback loop in which transcription factor continue to stimulate own expression
Wild type
An individual with the normal phenotype.
Mutant allele
Caused by a mutation in the DNA of the wild type allele
Histone acetyltransferases effect on chromatin compaction
DNA is - charged while histones are + charged. The covalent attachment of acetyl group decreases the amount of + charge of histone proteins and therefore decrease the binding of DNA and histone. Acetylation may attract other proteins to region that loosen chromatin compaction.
Explain how DNA methylation and formation of DNA loop control the expression of the Igf2 gene in mammals. how is this gene imprinted so that only the parental copy is expressed in offspring?
ICR and DMR in oogenesis is not methylated, so CTCF cab bind to these site to form a loop. Loop prevents nearby enhancer from activating the Igf2 gene. During sperm production, methylation of there site prevents CTCF binding and thereby prevents loop formation. Nearby enchancer activated Igf2 gene. Therefore copy of Igaf2 gene is inherited from father via sperm is active
DNA Methylation effect on Epigenetic Gene Regulation
Methyl groups attachment near promoters will inhibit transcription
Insulator
Segment of DNA that functions as boundary of two genes. Protects and insulates gene from regulatory effects of neighboring gene.
Point mutations
Silent Missense Nonsense Frameshift chemical changes in just one base pair of a gene
Covalent histone modification effect on Epigenetic Gene Regulation
Specific amino acid side chains found at amino terminal tails of histones may covalently modified (acetylated or phosphorylated) and could inhibit/enhance transcription
Define epigenetics. Are all epigenetic changes passed from parent to offspring? Explain.
Study of mechanisms that lead to changes in gene expression that can be inheritable and are reversible, but do not change DNA sequence. Not all epigenetic changes are passed, esp. if it is in a somatic cell.
Intergenic supressor
Supressor mutation that occurs in a gene that is different from the gene containing the original mutation
Somatic mutation
Takes place in a body cell, can affect the organism, not passed on to the offspring.
DNA Methylation
The addition of methyl groups to bases of DNA after DNA synthesis. Inhibits initiation of transcription when occurs near promoter.
Random mutation theory
The fluctuation test performed by Luria and Delbrück and the replica plating experiments performed by Lederberg and Lederberg were consistent with the
What is a nuclosome-free region? Where are they typically found in a genome? How are nucleosome-free regions thought to be functionally important?
They are a region of the gene that has no nucleosomes and are normally found at the core promoter or at the beginning or end of a gene. The beginning NFR is important so gene can be activated. End NFR important for proper termination.
Lethal mutation
a gene or chromosomal mutation that influences the development of an organism in such a way that the organism cannot survive
Induced mutation
a mutation caused by external agents such as mutagenic chemicals or radiation
Reversion mutation
a mutation that can be mutated a second time to revert DNA to it's original sequence
Spontaneous mutation
a random change in the DNA arising from errors in replication that occur randomly
Down promoter mutation
reduces affinity for regulatory factors, decreases rate of transcription