histone acetylation

Meaning: Histone tails are rich in lysine, whose side chain is positively charged (NH₃⁺) at physiological pH. That charge attracts the negatively charged phosphate backbone of DNA and helps hold nucleosomes in tightly packed chromatin. A histone acetyltransferase (HAT) moves an acetyl group from acetyl-CoA onto the lysine amino group, forming a neutral amide. With the charge gone, the histone grips DNA less tightly, chromatin opens (euchromatin), and transcription factors and RNA polymerase can reach the promoter. Histone deacetylases (HDACs) remove the acetyl group, restore the positive charge, condense chromatin (heterochromatin), and generally lower gene expression. This is an epigenetic mark: it is reversible and does not change the DNA sequence.

On the MCAT: A passage may show that a drug inhibiting HDACs raises expression of a gene, or that acetylated histones are found at actively transcribed promoters. You predict the direction: more acetylation, looser chromatin, more transcription. It is often paired with DNA methylation, which generally represses transcription.

Common confusion: Students say acetylation adds a negative charge or silences genes. It removes a positive charge, and that weakens binding to DNA. Do not mix it up with DNA methylation of cytosine, which generally silences genes.