eukaryotic epigentics Flashcards
how does a CPG island avoid being methylated?
has boundary elements which can exclude DNMTs from dna via barrier action, preventing enzyme progression
> physically block
apart from in CpG islands, why are CG dinucleotides so infrequent?
in their methylated form they are unstable and can spontaneously deaminate to a thymine residue
how can CPG-islands regulate gene expression?
leptin: methylation of CPG island can downregulate transcription
GLUT4: methylation of dinucleotides can block TF binding sites
describe the relationship between aging and epigentics
age - increase in global demethylation and increased in methylation in Cpg islands
Could increase risk of cancer
in cancer - hypermethylation of tumour suppressor genes at their promoters like p16 and VHL will silence those genes and promote tumourgenesis
also mice with mutations in DNMT1 have been shown to be at more risk of developing cancer as it can contribute to genomic instability
define epigenetics
heritable changes in gene function that DO NOT affect the DNA sequence itself (not a mutation), instead DNA is chemically modified
> way that genes can be regulated as it can control how and when a gene is transcribed!
underpins cell differentiation!
name some general epigenetic mechanisms
methylation - of histones
methylation - of DNA (CG dinucleotides)
these are covalent modifications to the DNA
why enzyme catalyses methylation
DNA methyltransferase covalently modifies DNA
how does plant methylation differ?
instead of CG sites, its CNG/CNN postitions so slightly more flexible
describe the roles of various DNA methyltransferases in maintaining epigentic modification
> DNMT1 has a preference for hemimethylated DNA and methylates the newly synthesised strand
> DNMT 3a,b,l involved in denovo methylation/ gene silencing processes
(seen in paternal and maternal genomes)
how can we REMOVE methyl groups?
DNMT1 can passively demethylate by forgetting to maintain methylation on newly synthesized DNA strands so following a few rounds of cell division these methylation marks are lost
or use TET enzymes (1,2,3) to actively demethylate
which gene encodes maintenence DNA ?methylase
A DNMT3L
B DMNT1
C DNMT3A
D DNMT3B
OPTION B
DNMT1 has a preference for hemi-methylated DNA so able to maitain the methylation marks onto daughter strand of DNA
name some general epigenetic mechanisms
methylation - of histones
methylation - of DNA (CG dinucleotides)
these are covalent modifications to the DNA
What are CpG islands?
Areas rich in unmethylated CpGs over 200bp long.
They can act as promoters and associated with housekeeping genes which remain unmethylated in germline and are genomically stable
why are CpG islands associated with housekeeping genes?
these consituitvely active genes have transcriptional machinery associated with gene promoter and so this prevent DMNT access to CpG island
what are canyons?
low methylated but highly conserved extended regions enriched in TF binding sites
> can contain multiple CpG islands
