Regulation of gene expression References: 1. Stryer: “Biochemistry”, 5th Ed. 2. Hames & Hooper: “Instant Notes in Biochemistry”, 2nd Ed. 1. Basic principles of gene control What is gene expression? It is a process by which a gene's information is converted into the structures and functions of a cell. For a protein encoding gene, it is a process of the transcription of a gene into mRNA, and the latter is translated into protein. How to control gene expression? In prokaryotic cells, gene expression is regulated primarily at the level of transcription by metabolites; In eukaryotes it is controlled by much more complex mechanisms, including the action of protein factors, hormones, etc. Control of gene expression in prokaryotes Structural gene R DNA R mRNA Enzyme Product Substrate Control of gene expression in eukaryotes Transcript. control 1 DNA Nucleus RNA synthesis 2 RNA processing control RNA transport control 3 mRNA Inactive mRNA Cytosol 5 mRNA degradation control mRNA Protein activity control 6 Translation 4 control Protein Inactive Protein 2. Regulation of Prokaryotic gene expression– the operon theory Operons are groups of genes that function to produce proteins needed by the cell. There are two types of genes in operons A. Structural genes code for proteins needed for the normal operation of the cell. B. Regulator genes code for proteins that regulate other genes. Lactose Operon PlacI lac I Plac Olac lac Z lac Y lac A Plac : promoter; Olac: operator; lac Z: b-galactosidase; lacY: permease; Lac A: transacetylase; lac I: structural gene for lac repressor; PlacI : promoter for lac I. Regulation of the lac operon in E. coli. p i Repressor mRNA Repressor The lact Operon p o y z a The repressor binds to the operator region and prevents RNA polymerase from transcribing the structural genes In the presence of lactose p Repressor mRNA i The lact Operon p o y z a mRNA b-galactosidase permease transacetylase Repressor Lactose Lactose binds the repressor and allows RNA polymerase access to the operator, resulting in transcription of the structural gene In the presence of glucose & lactose glucose Adenylcyclase cAMP p i ATP The lact Operon p o y z a Lactose Low level of transcription In the absence of glucose and presence of lactose CAP Adenylcyclase cAMP p i ATP The lact Operon p o y z active a Lactose High level of transcription CAP: catabolite activator protein Tryptophan Operon The trp operon encodes the genes for the synthesis of tryptophan Genes for enzymes P,O L a E D C B A P: promoter, O: operator, a: attenuator, L: leader sequence, A,B,C,D,E: enzymes of the Trp pathway Regulation of the trp operon in E. coli. Binding of Trp to the trp repressor increases the activity of the repressor, and therefore Trp is known as a corepressor. Expression of the trp operon is also regulated by attenuation. The attenuator region contains tandem Trp codons, which play a role to attenuate the transcription of the following genes. Regulation of the trp operon