DNA methylation Flashcards
Why are mCs mutagenic?
If deaminated -> T. If it was just C-> U which is identifiable but T are dsDNA bases.
Cpg islands
at least 200bp long and are highly enriched for CpGs. They are usually between 300
and 1500bp long. CpG methylation at promoters correlates very strongly with
repression of the associated gene.
what kind of genes have CpG islands
most often housekeeping ones, other genes as well but generally not tissue specific. Tissue-specific genes have to be activated essential once so risking to keep mCs for so long to keep them silenced beforehand could lead to mutations.
Why would CGIs be used if they stay unmethylated the whole time for housekeeping genes?
they still facilitate the binding of TFs, transcription machinery so on.
necessary enzymes for de novo methylation
DNMT3A and B. DNMT3L as well but it is not really a methyl transferase.
enzyme used to copy methylation patterns to newly formed strand during replication
DNMT1, it scans through the newstrand-oldstrand hybrid, and everytime it detects a
methylated CG, it methylates the C on the GC dimer of the complementary strand (the
newly synthesized strand)
Role of demethylation waves
During germ cell development, the cells
need to forget their ‘somatic’ past to become germ-cell like, which has many
characteristics of a pluripotent cell. After fertilization, the pronuclei need to forget
their ‘gametic’ past to become totipotent, to be able to generate an entire body, all
cell types in the body.
how many waves of demethylation
2
Paternal demethylation after fertilization is an active process, T/F
True
Maternal demethylation after fertilization is an active process, T/F
False, they just dont maintain the methylations
two mechanisms mCpG exert repressive role on gene expression
Methylated CpGs will be bound by Methyl binding proteins (MBDs) that will recruit
HKMTs that will put methylation marks on H3K27 (a repressive mark). It will also
recruit histone deacetylases (HDACs) that will remove acetyl marks from histone (an
activating mark). Both outcomes are repressive. MBDs also inhibit or prevent binding
of the RNA pol II preinitiation complex, resulting in less RNA pol II binding preventing
transcription.