BioH Chapter 14 – Control over Genes

Control of Gene Expression Cells are selective about which genes they require This depends upon:  Cell type  Specific cell activity at the moment of need  External chemical signals received  Built-in internal chemical signals Two main systems of control:  Negative feedback  Positive feedback Systems use: regulatory proteins, hormones, other molecules

Escherichia coli Bacterial Cell Gene Control

Negative transcription control – lac operon Promoter sequence – base sequence signaling the start of a gene Operator sequence – between promoter & genes, binding site for repressor Repressor protein – regulatory protein that can block transcription of genes Operon – arrangement where promoter and operator control more than one gene

Low lactose concentration – Repressor is free to block transcription (RNA polymerase cannot bind) With low concentrations of lactose, the regulator gene produces repressor proteins that bind at the operator site, blocking the promoter sequence form starting the production of lactose digesting enzymes. (Negative control)

High lactose concentration – lactose induces transcription by binding to the repressor (distorting the shape) so that is cannot bind to the operator site. The promoter is exposed and transcription occurs producing lactose-digesting enzymes.

Negative transcription control summary (E.coli lactose operon) Low lactose concentration does not allow lactose-degrading enzymes to be produced by allowing the repressor protein to bind at the operator site, preventing RNA polymerase from binding. High lactose concentration allows some lactose molecules to bind to the repressor proteins, keeping them from binding to the operator. This allows RNA polymerase to bind to the promoter site, causing transcription of the lactose-degrading enzymes. They are produced only when there is a high enough concentration of lactose.

Positive transcription control summary (E.coli and glucose) CAP is activated by cAMP (produced from ATP, with low concentrations of glucose) High glucose concentration –Low cAMP –CAP does not adhere to lactose promoter –Almost no lactose degenerating enzymes Low glucose concentration with high lactose conentration –cAMP accumulates –CAP adheres to lactose promoter, allowing lactose metabolizing enzymes to form E. Coli pays far more attention to glucose than to lactose, producing more enzymes for glucose digestion and at a much faster rate. In fact, the lactose operon isn’t used much – unless glucose is absent. When no glucose is present in the bacterium, CAP, an activator protein, acts upon the lac operon by helping RNA polymerase to bind to the promoter sequence.

Eukaryotic cell gene controls Cell Differentiation Even though all somatic cells contain the same DNA as found in the fertilized egg, nearly all cells become specialized in composition, structure and function = cell differentiation. So, genes specifying proteins need to be very specific for the cell in which they occur. It is estimated that only 5-10% of the genes found in a cell are used at any given time.

Eukaryotic Gene Control Signaling Mechanisms - Hormones  Have positive or negative control in target cells  Modify enhancers – base sequences in DNA that act as binding site for specific activator proteins

 In multicellular organisms, gene controls underlie basic, short-term housekeeping cellular tasks as well as more intricate long-term patterns of bodily growth and development.  As cells differentiate, some suppress certain genes not necessary for cell function.  Hormones and other environmental signals influence gene expression inside the cells. Eukaryotic Cell Gene Control Overview

Levels of Gene Expression Control  Basic, “housekeeping” tasks – under control of positive system control (continuous and low levels)  Homeostatic systems – much more complex and involve many cells – under fluctuating positive and negative systems control  Both before and after transcription occurs  All control systems must be highly coordinated to allow multicellular interaction

Out of control  Cells go through their life cycles in very controlled/regulated manner  Regulatory proteins control onset of activities timing amount of activity response to external & internal stimuli  If a cell lacks these proteins (due to mutated genes not transcribing correct, or any, molecules), then the cell is deprived of crucial proteins – may result in cancer

Normal Cell Cycle Protein kinases – enzymes that control passage of cells through life cycle by controlling phosphate group attachment. Operate between G1 and S phase and G2 to mitosis

Cancer Cell Characteristics  Cell’s plasma membrane & cytoplasm change dramatically Membrane is more permeable Proteins lost or altered, abnormal ones are formed Cytoskeleton disorganizes, shrinks, or both Enzyme activity accelerates  Cancer cells grow & divide abnormally Overpopulation controls are lost Cell populations reach high densities Enzymes trigger increased blood vessels in area  Cancer cells do not adhere to each other as normal cells do Inability to stay anchored to proper tissues  Cancer cells are lethal – if not eradicated, the organism eventually dies

Cell growth out of control Tumors –Do NOT respond to normal cell growth control (cell surface enzyme malfunction) –As long as conditions are favorable, cells grow and divide –Do NOT have correct repair machinery (DNA/RNA polymerase, ligase) Benign Tumor –Slow growth –Usually stay confined to original growth site Malignant Tumor –Rapid growth –Exhibits metastasis

Benign Tumors Normal Mole Cysts Malignant Tumors Malignant moles Cancerous cell progression

Malignant cancers The three most common cancers in men in the United States are: –Prostate cancer –Lung cancer –Colon cancer In women in the United States, the three most common cancers are: –Breast cancer –Colon cancer –Lung cancer