The DNA sequence never changes. Adding a methyl group (–CH₃) to cytosine bases in the promoter — the short "on switch" region just upstream of a gene — physically bulks up the groove that transcription-factor proteins and RNA polymerase need to grip. Enough methyl tags there and the binding machinery can no longer dock: no transcription factor, no RNA polymerase, no mRNA, gene silenced. Strip the methyl tags off and the same unmutated DNA becomes accessible again — binding resumes and mRNA output snaps back on.
bindChance = clamp(1 - methFraction / 0.5, 0, 1)
mRNA/s ∝ bindChance × (RNA-polymerase throughput)
gene state = ON if bindChance > 0
gene state = OFF if methFraction ≥ 0.5 (silenced)
- Click a cytosine tile — toggles that single CpG site between methylated (red, with a visible methyl tag) and unmethylated (blue).
- Transcription factors (violet) — repeatedly approach the promoter; watch them bounce off when methylation is high, or dock cleanly when it's low.
- RNA polymerase (teal) — only recruited after a transcription factor docks; it then slides along the gene body streaming out mRNA (orange) behind it.
- Tumor-suppressor scenario — the same mechanism, applied to a gene that normally restrains cell division: abnormal promoter methylation silencing it is a recurring driver event in cancer.
Real-world relevance: this is exactly how genes like BRCA1 or MLH1 get epigenetically silenced in tumors even when their coding sequence is completely normal — and why demethylating drugs (e.g. azacitidine, decitabine) can reactivate silenced tumor-suppressor genes as cancer therapy.