Overview Conducting the Genetic Orchestra Prokaryotes and eukaryotes alter gene expression in response to their changing environment In multicellular eukaryotes gene expression regulates development and is responsible for differences in cell types RNA molecules play many roles in regulating gene expression in eukaryotes In Prokaryotes natural selection has favored bacteria such that they produce only the products needed by that cell A Prokaryotic cell can regulate the production of enzymes by feedback inhibition or by gene regulation Gene expression in bacteria is controlled by the operon model Copyright 2008 Pearson Education Inc publishing as Pearson Benjamin Cummings Fig 18 2 Precursor Feedback inhibition trpE gene Enzyme 1 trpD gene Regulation of gene expression Enzyme 2 trpC gene trpB gene Enzyme 3 trpA gene Tryptophan a Regulation of enzyme activity b Regulation of enzyme production Operons The Basic Concept A cluster of functionally related genes can be under coordinated control by a single on off switch The regulatory switch is a segment of DNA called an operator usually positioned within the promoter An operon is the entire stretch of DNA that includes the operator the promoter and the genes that they control The operon can be switched off by a protein repressor The repressor prevents gene transcription by binding to the operator and blocking RNA polymerase The repressor is the product of a separate regulatory gene Copyright 2008 Pearson Education Inc publishing as Pearson Benjamin Cummings Fig 18 3a trp operon Promoter Promoter DNA trpR Regulatory gene mRNA 5 Protein Genes of operon trpE 3 Operator Start codon mRNA 5 RNA polymerase Inactive repressor trpD trpC trpB trpA B A Stop codon E D C Polypeptide subunits that make up enzymes for tryptophan synthesis a Tryptophan absent repressor inactive operon on E coli can synthesize the amino acid tryptophan By default the trp operon is on and the genes for tryptophan synthesis are transcribed Fig 18 3b 1 DNA No RNA made mRNA Protein Active repressor Tryptophan corepressor b Tryptophan present repressor active operon off A corepressor is a molecule that cooperates with a repressor protein to switch an operon off Fig 18 3b 2 When tryptophan is present it binds to the trp repressor protein which turns the operon off DNA No RNA made mRNA Protein Active repressor Tryptophan corepressor b Tryptophan present repressor active operon off The repressor is active only in the presence of its corepressor tryptophan thus the trp operon is turned off repressed if tryptophan levels are high Concept 18 2 Eukaryotic gene expression can be regulated at any stage All organisms must regulate which genes are expressed at any given time In multicellular organisms gene expression is essential for cell specialization Almost all the cells in an organism are genetically identical Differences between cell types result from differential gene expression the expression of different genes by cells with the same genome Errors in gene expression can lead to diseases including cancer Gene expression is regulated at many stages Copyright 2008 Pearson Education Inc publishing as Pearson Benjamin Cummings Fig 18 6 Signal NUCLEUS Chromatin Chromatin modification DNA Gene available for transcription Gene Transcription RNA Exon Primary transcript Intron RNA processing Tail Cap mRNA in nucleus Transport to cytoplasm CYTOPLASM mRNA in cytoplasm Degradation of mRNA Translation Polypeptide Protein processing Degradation of protein Active protein Transport to cellular destination Cellular function Regulation of Chromatin Structure Genes within highly packed heterochromatin are usually not expressed Chemical modifications to histones and DNA of chromatin influence both chromatin structure and gene expression In histone acetylation acetyl groups are attached to positively charged lysines in histone tails This process loosens chromatin structure thereby promoting the initiation of transcription The addition of methyl groups methylation can condense chromatin the addition of phosphate groups phosphorylation next to a methylated amino acid can loosen chromatin Copyright 2008 Pearson Education Inc publishing as Pearson Benjamin Cummings Fig 18 7 Histone tails Amino acids available for chemical modification DNA double helix a Histone tails protrude outward from a nucleosome Unacetylated histones Acetylated histones b Acetylation of histone tails promotes loose chromatin structure that permits transcription Copyright 2008 Pearson Education Inc publishing as Pearson Benjamin Cummings DNA Methylation DNA methylation the addition of methyl groups to certain bases in DNA is associated with reduced transcription in some species DNA methylation can cause long term inactivation of genes in cellular differentiation In genomic imprinting methylation regulates expression of either the maternal or paternal alleles of certain genes at the start of development Copyright 2008 Pearson Education Inc publishing as Pearson Benjamin Cummings Concept 18 3 Noncoding RNAs play multiple roles in controlling gene expression Only a small fraction of DNA codes for proteins rRNA and tRNA A significant amount of the genome may be transcribed into noncoding RNAs Noncoding RNAs regulate gene expression at two points mRNA translation and chromatin configuration 1 The noncoding RNAs that regulate mRNA translation are MicroRNAs miRNAs these are small single stranded RNA molecules that can bind to mRNA These can degrade mRNA or block its translation Copyright 2008 Pearson Education Inc publishing as Pearson Benjamin Cummings 2 The noncoding RNAs that regulate chromatin configration are small interfering RNAs siRNAs these are small double stranded RNA molecules that can bind to and block large regions of the chromosome Both of these miRNAs and siRNAs inhibit gene expression by targeting the RNA molecules in a process known as RNA interference RNAi Copyright 2008 Pearson Education Inc publishing as Pearson Benjamin Cummings Concept 18 5 Cancer results from genetic changes that affect cell cycle control The gene regulation systems that go wrong during cancer are the very same systems involved in embryonic development Cancer can be caused by mutations to genes that regulate cell growth and division Tumor viruses can cause cancer in animals including humans Oncogenes are cancer causing genes Proto oncogenes are the corresponding normal cellular genes that are responsible for normal cell growth and division