(Epi)genomics and cancer
8 important questions on (Epi)genomics and cancer
DNA methylation & gene expression
THUS...
- Promotor region often contains dense regions of CpG's = CpG islands
- Hypermethylation of CpG islands in promoter regions prevents binding of transcription factors
- = silencing of gene expression
- DNA methylation can regulate gene expression
In what other places does methylation occurs?
- Introns
- LINEs
- SINEs
- miscellaneous unique sequences
Global DNA methylation
- Repetitive elements such as tandem repeats and interspersed elements
- Scattered among the genome and in gene-poor regions
- Example: hypomethylation of LINE-1 = 17% of genome
THUS...
- DNA methylation can occur in the genes (gene-specific) or in the rest of the genome (global)
- A lack of methylation in global regions can result in genomic instability
- DNA methylation can regulate gene expression
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What are histone modifications?
Specific groups, for example, methyl groups can be added to the tails
The presents of these specific groups can determine when the chromatin has an open or closed structure. This also determines if the DNA is accessible or not.
And this is important for the binding of transcription factors that are need for the start of gene expression.
The accessibility of DNA. When is it closed and when is it open?
- transcription cannot occur
- Heterochromatin
Open DNA
- Transcription factors bind and induce gene expression
- Euchromatin
How can miRNAs regulate gene expression?
So also the miRNA determines whether a protein is present or not
A study of folic acid and gene-specific methylation found that
- N=86
- history of colorectal adenomas
- 6 months intervention
- 5 mg folic acid and 1.25 mg vB12
What are future perspectives [(epi)genomics]
- Large scale prospective studies
- Multiple levels (histone modification, DNA synthesis,..
Effects of folate on DNA methylation dose-, site- and tissue- specific and dependent on stage of disease and stage of life
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