G6 Flashcards
What is epigenetics
heritable changes in gene expression which persist through cell division and arent caused by changes in nt sequence
what are two examples of epigentic modifications
histone modifications - modifies chromatin to reguulate genes
DNA modification - methylation to repress expression of particular gnees.
what is downsyndrome an example of
trisomy of chromosome 21
what bases are methylated in mammals and prokaryotes
cs in mamamls
some As in prokartotes
what is chromatin
compaction of DNA via interactions with proteins, histones, forms chromatin, template for epigenetic modifications.
what is euhromatin
actively transcribed extended structure
what is heterochromatin
often highly repetative, condensed adn not transcribed, near centromeres and teleomeres (not 100% true as eg. y chromosome contains big chunks of heterochromatin
Where is DNA methylated in euks
methyl to fifth carbon of cytosine ring to form 5-methyl cytosine, mostly on CpG dinucleotide sites
how can methylation be potentially harmful if there is an elevated mutational rate
as CG >TG which could form CGA -> TGA which is a stop codon.
what percent of CPGS are methylated in mice
4%
what are CpG islands
regions with high frequency of CpG sites. - uneven distribution - clusters of CpGs (typically unmethylated) mark housekeeping active genes.
what is kind of mark is CpG methylation
generally repressive
reducing DNA binding of many proteins, binding site for methyl binding proteins, (MBD domain containing MeCP2)
what roles does DNA methylation play in development?
reg gene expression imprinting x inactivation differentation aging and cancer defence against transposons, viruses - downreg of expression of endogenous retrovirsues counteract recombination of repetative DNA important in chromosome segregation
What are the 5 DNA methytransferances
Dnmt1: maintainance methylation - counteracts dilution of methyl groups
Dnmt2- very little activity
Dnmt3a - de novo methylation: imprinting pericentric region satellites
Dnmt3b: de novo methylation: CpG islands and X chromosome
DnmttL: no enzymatic activity, reg subunit: imprinting
what id demethylation
direct removal of methyl group.
- via BER or NER
what is the intermediate before 5-methyl cytosine removal
5-hydroxy methyl cytosine
What is the CXXC domain
Binuclear Zn chelating domain found in several chromatin association proteins, which can discriminate between unmethyalted and methylated CpGs
Describe a nucelosome
147bp of DNA wrapped around an octamer of histones H2a, H2B, H3 and H4
assemebled as H3/H4 tetramere followed by addition of two H2A/H2B dimers.
where do you get most modification of histones
on linkers H1
- high levels of H1 = increasingly repressive
when is paternal imprinting often involved?
in the early stages of embryogenesis - maximises growth rate of embryo and resources it takes from the mother.
what is hypomethylation
inhibition of methylation
Why are tortoise shell cats always female
because ginger and black colours are on one x chromosome each, inactivation continues in descendent cells to give mottled pattern.
are all X linked genes subject to X inactivation on Xi?
no some genes are still active.
where does x inactivation occur?
somatic cells
but embryonic cells are XaXa
