Epigenetics Flashcards
(26 cards)
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.
What are the mechanisms of X chromosome inactivation?
At ~1000 cell stage (blastocyst) the cell chooses one X to remain ON. The other X is inactivated through XIST (Xinactivation-specific transcript) an X chromosome-encoded IncRNA. XIST cooats the CX chromosome leading to heterochromatin spreading (silencing) and methylation.
What is genome imprinting?
The parent-specific expression or repression of genes or chromosomes in offspring: even though two copies of a given gene are inherited (one from each parent) only the maternal or paternal allele is expressed. The non-expressed allele is said to be imprinted. In females certain sweat patches distributed randomly throughout the body. On X chromosome is allele for sweat gland production. Areas of the body where sweating is greater, caused by trhe activation of the paternal X chromosome. The non expressed allele is said to be imprinted.
What is a hinny?
Mother was a donkey and father was a horse: non-equivalent paternal contributions
Donkey 2N = 62
Horse 2N = 64,
hinney 2N = 63
What is a mule?
Mother horse and father donkey.
Donkey 2N = 62
Horse 2N = 64
Mule 2N = 63.
How many genes are imprinted in humans?
Over 70 imprinted genes: similar to the mouse. Deregulation of imprinted genes has been observed in human diseases. Characterised by non-mendelian inheritance patterns that exhibit parental-origin effects: the symptoms suggest a role of imprinted genes in growth regulation during embryonic and post-natal development, brain function and behaviour.
Which disease are associated with genomic imprinting?
Beckwith-Wiedemann syndrome Prader-Willi syndrome Angelman syndrome Wilms tumour Fragile X syndrome Myotonic dystrophy (congenital)
What is the significance of IGF2?
loss of imprinting of IGF2 is one of the most common molecular alterations in human cancers.
Describe Angelman syndrome
Severe mental retardation, microencephaly, lack of speech, frequent laughter. Deletion of maternal 15q11-q13 (loss or inactivation of maternal UBE3A gene)
Describe Prader-Willi syndrome
Mild mental retardation, obesity, short stature, deletion of paternal 15q11-q13 (deficient snoRNAs expression of paternal alleles)
