Epigenetics: DNA and histone methylation !

Epigenetics means chemical marks on DNA and histones that switch genes on or off without changing the sequence, and that pass on when cells divide.

Updated 2026-11-01

Key facts

DNA methylation: cytosine in CpG dinucleotides becomes 5-methylcytosine (DNMT, donor SAM). Methylated promoter = silenced gene.
Histone acetylation (HAT): opens chromatin and activates genes. Deacetylation (HDAC): closes it and silences them.
Histone methylation: activates or silences depending on the residue (H3K4me3 activates; H3K9me3 and H3K27me3 silence).
Genomic imprinting: some genes are expressed only from the paternal or the maternal allele (Prader-Willi, Angelman).
X inactivation: in women one X is silenced at random by XIST RNA (Barr body).

DNMT3A/3B add new methyl marks; DNMT1 copies the pattern onto the daughter strand after replication (maintenance).
TET enzymes oxidise 5-methylcytosine and allow the mark to be removed (active demethylation).
Bromodomain proteins 'read' acetylation; chromodomain proteins read histone methylation.
MicroRNAs (about 22 nt, in the RISC complex) silence mRNAs by degradation or translational block: another layer of control.
Diet (folate, B12, choline, methionine) supplies methyl groups through S-adenosylmethionine.
Typical of cancer: global hypomethylation and hypermethylation of tumour-suppressor promoters (MLH1, p16, BRCA1).

Epigenetic drugs: azacitidine and decitabine (hypomethylating) in myelodysplastic syndromes; HDAC inhibitors (vorinostat) in T-cell lymphomas.
In fragile X syndrome the CGG expansion leads to methylation of the FMR1 promoter and silences the gene.
In sporadic MSI colorectal cancer the most common cause is MLH1 promoter hypermethylation, not an inherited mutation.

Think of the answer, then tap the question to see it.

What does methylation of CpG islands in a promoter do?

It silences the gene: it blocks transcription-factor binding and recruits proteins that compact chromatin.

Which enzyme maintains the methylation pattern after replication?

DNMT1, which copies the methylation from the old strand to the new one.

How does histone acetylation affect gene expression?

It neutralises the positive charge of lysines, loosens DNA binding and opens chromatin: transcription increases.

What mechanism silences one X chromosome in women?

The non-coding RNA XIST coats the chosen X and packs it into heterochromatin (Barr body).

Educational information, not medical advice. For any symptom, see a health professional.

Sources: What is epigenetics?: MedlinePlus Genetics (MedlinePlus, US National Library of Medicine, 2026); Epigenetic regulation of gene expression (Reactome, 2026); Chromatin organization (Reactome, 2026); Textbook of Biochemistry for Medical Students, 6th ed. (Jaypee Brothers Medical Publishers (Vasudevan DM, Sreekumari S, Vaidyanathan K), 2011).

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Representative model, for educational purposes only.