Epigenetics Flashcards
Define epigenetics.
The study of reversible heritable changes in gene function that occur without a change in the sequence of DNA.
Adrian Bird’s definition: the structural adaptation of chromosomal regions so as to register, signal or perpetuate altered activity states.
What qualifies as an epigenetic mark?
Alterations that last less that one cell cycle do not qualify as epigenetic under the definition that strictly requires heritability whereas non-mutational changes that are transmitted from one cell to its daughters or between generations of an organism do qualify.
What are the mechanisms of epigenetics?
Histone modifications and chromatin remodelling.
DNA methylation and acetylation
Non-coding RNA-mediated regulation
What is DNMT1 and its function?/ What is the histone code hypothesis
DNA methyltransferase 1 which follows the replication fork adding methylation marks to newly synthesised DNA to re-establish histone modifications. These specific modifications are associated with specific functions.
How many histone proteins are there?
Four
In amino acid number 9 which epigenetic marks can be found?
A lycine, can be acetylated which causes histone deposition, condensation of histone and gene silencing. If methylated gene silencing and heterochromatin formation That region of the genome will not be expressed in that cell type.
Which is the best understood example of epigenetic gene regulator?
DNA methylation
Describe how direct DNA methylation occurs in vertebrates.
Cytosine of CpG islands are common sites for methylation: 70-80% methylated CG in mammals however CGs do not occur that often in our genome.
Describe DNA methylation in plants.
CpG, CpNpG and CpHpH (H=A/T/C) and methylation of C is common in plants but rare for mammals:
5-hydroxymethylcytosine
5-formylcytosine
5-carboxylcytosine exist:
It is not clear what the function is,. however it could be implicated in DNA degradations. They occur frequently in stem cells.
In which processes does methylation occur?
Embryonic development
X chromosome inactivation
Imprinting: DNA methylation
Gene silencing
Describe the degree of DNA methylation in the germ line.
primordial germ cells have their epigentic settings erased for gonadal differentiation. Once germ cells start developing, de novo methylation and establishment of imprinting marks occurs: sperm have greater degree of methylation than ova.
Once fertilisation occurs, what happens to epigenetic marks?
There is demethylation in the early embyro; largely of the father’s epigenetic marks. The mothers epigenetic marks persist through the morula stage until the early blastocyst stage where there a little if any epigenetic marks. Once pregastrulation occurs, de novo methylation occurs in somatic cells as well as in the trophoblast lineages to form somatic cells and the placenta/yolk sac respectively.
What is the evolutionary benefit of epigenetic marks?
It enables the genome to respond quickly to the environment.
Describe an example of epigenetics during embryonic development.
Agouti gene: mutation causes both obesity and agouti coat colour. A small % of genetically identical litter mates that show this wild-type phenotype. Mothers fed on bisphenol A containing diet have litters with a higher proportion of obese agouti mice. These agouti mice have 31% less methylation at agouti locus than brown littermates –> an epiphenotype.
A diet containing methyl-rich foods (Colchicine, folic acid, vitB12) promoted greater methylation of agouti gene: mostly brown healthy mice.
How are calico cats an example of epigenetics?
The early female embryo has both X chromosomes active, at some time during the late blastocyst stage, one of the X chromosomes are inactivated. Which one is inactivated is entirely random. Methylation patterns are heritable through mitosis but reset during oogenesis. Fully developed female is a mosaic of different clones. Random = every calico cat has a different pattern. Biomedical example of X chromosome inactivation is Anhydrotic dysplasia mosaicism.
