DNA methylation - 5mC
18 important questions on DNA methylation - 5mC
What are the 5mC targets and non-targets?
- Cytosines - mainly CG in mammals, CG, CHG, CHH in plants and no C methylation in Drosophila
- Transposable element and other repeated sequences
- gene bodies
- Linker DNA
Non-target: H3K4 methylation, TSS and active regulatory sequences, CpG
Why is there more 5mC in large genomes than in small?
What is gene body methylation?
- H3K36me3 is added to histones behind RNA pol
- Dnmt3b binds to H3K36me3 and adds methylation to gene body
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What is the function of DNMT3?
De novo methyltransferase DNMT3 methylates linker DNA through binding of unmethylated lysine of histone H3
What is the function of H3K4me and how is it related with 5mC?
H3K4me prevents de novo DNA methyltransferase to do its job
- H3K4me is present at TSS
How are genes still transcribed if there is gene body methylation?
How are CpG island protected against 5mC?
- Binding of TF
- presence of H3K4me
- binding H3K4 methyltransferases
- Presence enzymes involved in DNA demethylation (TET enzymes)
- Absence nucleosomes
What happens if CpG islands were methylated?
How are 5mc profiles used to identify distant transcriptional enhancer?
- binding of pioneer TF can result in LMRs by DNA demethylation
- Unmethylated regions are enriched at CpG and promotors
What are the roles of 5mC?
- keep TEs under control
- prevent homologous recombination
Gene regulation
- genomic imprinting in plants & mammals
- X-chromosome inactivation in female mammals
- role in regulation of gene transcription
- tissue-specific activation of regulatory sequences involves DNA demethylation
Why is it needed that transposons to be controlled?
- insertional mutagenesis
- homologous recombination
- gene respression by proximity to silenced transposon sequences
- Transcription interference and RNA interference
Why are TE insertions often in DNA regions that commonly mutate in cancer cells?
Why is DNA methylation required for genomic imprinting?
- a given gene is alway imprinted in same manner
- monoallelic expression of imprinted genes requires 5mC im mammals and plants
What is the role of X-inactivation in X-chromosoom in females?
- in absence of 5mC, the inactive X can be reactivated again
What is the role of 5-hydroxymethylation?
What is the difference between de novo DNA methylation and maintenance DNA methylation?
- de novo enzymes add methylation to unmethylated DNA, maintenance enzymes maintain DNA methylation during replication
- During development 5mC patterns are established by de novo methyltransferases DNMT3A and DNMT3B, and subsequently maintained through mitotic cell divisions by maintenance methyltransferase DNMT1
Which enzymes mediate DNA methylation?
- asymmetric methylation can occur in presence of high expression de novo methyltransferases
How is piRNA involved in 5mC?
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