Why genes are regulated Organisms respond to environment - e.g. nutrients available Multi-cellular organisms must have different cell types (differentiation) Genes must be switched on/off at correct times and in correct cells Gene regulation is complex and precisely controlled process

DNA does not change All cells in an organism have the same set of genes (usually) DNA sequence does not change but genes can be switched on/off Gene regulation must be a reversible process Some gene activities are required in all cell types (housekeeping genes) e.g. synthesis of RNA Others are tissue specific e.g. to make muscle proteins (myosin, actin) in muscle cells

Any cell has all genes to make frog Adult frog Unfertilised egg Skin cell removed and cultured Destroy nucleus by UV light Nucleus removed and micro-injected into egg Normal embryo Normal tadpole

Regulation at what stage? DNA RNA Protein Transport, Processing transcription translation Active protein Several places at which regulation could occur Mostly regulated at transcription stage Most economical - don’t make things that aren’t needed Achieved by specific proteins that bind to DNA

DNA binding proteins Specific proteins bind to specific points in the DNA The two fit together like a lock and key Almost all genes are regulated this way DNA Protein

Gene regulation in bacteria Simple systems to turn genes on and off Response to nutrients e.g. if tryptophan (an amino acid) is in the medium, don’t need to make your own Similar systems exist for other amino acids Turning a gene off is repression

Tryptophan (trp) gene regulation Trp operon promoter E D C B A trp synthesis enzymes DNA RNA No trp Trp present Repressor protein RNA polymerase No transcription

Gene activation Bacteria turn on genes to use sugars for energy when available Turning genes on is activation Also uses specific DNA-binding proteins protein DNA RNA RNA polymerase Activator Environmental stimulus Promoter

Gene regulation in eukaryotes Genes have to be switched on by regulatory proteins, otherwise would do nothing General proteins in all cell types, special ones in specific cell types Regulatory proteins bind to sites in DNA called enhancers Enhancers can be 1000s of bp away from gene

Gene regulation in eukaryotes Specific activator protein Promoter Enhancer RNA polymerase & general transcription factors

Drosophila eye development Cells for eye Cells for leg Larva Adult Normal Ey gene artificially expressed in cells for leg “Eye” on leg