eukaryotic gene regulation

Meaning: Eukaryotic DNA is wrapped on histones in chromatin, so access comes first. Histone acetylation neutralizes lysine's positive charge, loosens DNA binding, and favors transcription (euchromatin). DNA methylation, typically at cytosines in CpG islands, generally silences genes (heterochromatin). Next is initiation: general transcription factors and RNA polymerase II assemble at the promoter, while specific transcription factors bind enhancers or silencers, which can lie far from the gene. DNA looping brings them to the promoter. Later controls include alternative splicing, mRNA stability, microRNAs, and protein modification or degradation.

On the MCAT: Expect a passage with a mutated enhancer, a transcription factor knockout, or a drug that changes acetylation or methylation, and you predict whether expression rises or falls. Steroid hormones are a common example: they enter the cell and bind intracellular receptors that act as transcription factors. Questions may also ask you to contrast this with the bacterial lac operon.

Common confusion: Students apply the operon model to eukaryotes. Eukaryotic genes usually have their own promoters, and an mRNA typically encodes one protein. Also keep the two chemical marks straight: histone acetylation generally activates, while DNA methylation generally represses.