Regulation of gene expression

Chromatin level (epigenetic): histone acetylation by HATs loosens chromatin and favours transcription, deacetylation by HDACs condenses it; histone methylation can activate or repress depending on the residue. DNA methylation of cytosines in CpG islands of promoters (by DNMTs) silences genes stably through cell divisions. These marks underlie X-inactivation (XIST RNA coats the inactive X) and genomic imprinting (expression of only the maternal or paternal allele).

Transcriptional level: sequence-specific transcription factors (zinc-finger, helix-turn-helix, leucine-zipper, helix-loop-helix families) bind promoters and enhancers and recruit or block co-activators and the transcription machinery. Combinations of factors define cell identity (e.g. MyoD in muscle). Signals regulate transcription factors by phosphorylation, ligand binding (nuclear hormone receptors) or controlled nuclear entry (NF-κB, SMADs, STATs).

Post-transcriptional level: alternative splicing, regulated mRNA stability and localisation, microRNAs (≈22-nucleotide RNAs that guide the RISC complex to block translation or degrade target mRNAs) and translational control (e.g. iron-responsive elements: low iron increases ferritin translation and stabilises transferrin-receptor mRNA). Post-translational level: phosphorylation, proteolytic activation and ubiquitin-mediated destruction. (In bacteria, genes are often grouped in co-regulated operons such as the lac operon — absent in humans.)