Chapter 7 Control Of Gene Expression PDF

Chapter 7 Control of Gene Expression Copyright © 2022 W. W. Norton & Company, Inc. The Different Cell Types of a Multicellular Organism Contain the Same DNA Different Cell Types Synthesize Different Sets of RNAs and Proteins The Different Cell Types of a Multicellular Organism Contain the Same DNA T...

Chapter 7 Control of Gene Expression Copyright © 2022 W. W. Norton & Company, Inc. The Different Cell Types of a Multicellular Organism Contain the Same DNA Different Cell Types Synthesize Different Sets of RNAs and Proteins The Different Cell Types of a Multicellular Organism Contain the Same DNA The genome of a cell contains in its entire DNA sequence the information to make many thousands of different protein and RNA molecules. A cell typically expresses only a fraction of its genes, and the different types of cells in multicellular organisms arise because different sets of genes are expressed. All cells can change the pattern of genes they express in response to changes in their environment, such as signals from other cells. The regulation of gene expression is thus crucial for life. For most genes, it is the initiation of RNA transcription that provides the most important point of control. External Signals Can Cause a Cell to Change the Expression of Its Genes. Gene Expression Can Be Regulated at Many of the Steps in the Pathway from DNA to RNA to Protein Control of Transcription By Sequence Specific DNA Binding Proteins Transcription regulators recognize cis-regulatory sequence (5-12 nucleotides pairs in length) which lie close to the gene usually upstream. Binding to these sequences specify which genes are to be transcribed and at what rate. Approximately 10% of the protein-coding genes of most organisms are devoted to transcription regulators, making them one of the largest classes of proteins in the cell. A given transcription regulator typically recognizes a specific cis-regulatory sequence that is different from those recognized by the other transcription regulators in the cell. The positions, identity, and arrangement of cis-regulatory sequences that ultimately determine the time and place that each gene is transcribed. Nearly all transcription regulators make the majority of their contacts with the major groove; wider and displays more molecular features than the minor groove. Transcription Regulators Contain Structural Motifs That Can Read DNA Sequences Dimerization of Transcription Regulators Increases Their Affinity and Specificity for DNA A monomer of a typical transcription regulator recognizes about 4–8 nucleotide pairs of DNA, does not bind tightly to a single DNA sequence. The DNA sequence recognized by a monomer does not usually contain sufficient information to be picked out from the background of such sequences that would occur at random across the genome. Many transcription regulators form dimers, with both monomers. This arrangement doubles the length of the cisregulatory sequence recognized and greatly increases both the affinity and the specificity of transcription regulator binding. Heterodimers can form between two different transcription regulators, and this configuration also increases both affinity and specificity. Some transcription regulators can form heterodimers with more than one partner protein; in this way, the same transcription regulator can be “reused” to create several distinct DNA-binding specificities Many Transcription Regulators Bind Cooperatively to DNA Cooperative binding means that, over a range of concentrations of the transcription regulator, binding is more of an all-or-none phenomenon than for noncooperative binding; that is, at most protein concentrations, the cis-regulatory sequence is either nearly empty or nearly fully occupied and is rarely somewhere in between DNA-Binding by Transcription Regulators Is Dynamic The binding of transcription regulators is highly dynamic, with transcription regulator molecules in constant motion, rapidly binding and dissociating from DNA. In most cases a given transcription regulator molecule stays on its cis-regulatory sequence for only a short time, but it is rapidly replaced by other molecules of the same regulator. Thus, when we consider a cis-regulatory sequence being fully bound by its matching transcription regulator, this state is an average, over time, of many individual association and dissociation events Bacteria regulate the expression of many of their genes according to the food sources that are available in the environment. These genes are arranged in a cluster on the chromosome and are transcribed from a single promoter as one long mRNA molecule; such coordinately transcribed clusters are called operons. operons are common in bacteria but rare in eukaryotes, where genes are typically transcribed and regulated individually The Tryptophan Repressor Switches Genes Off Tryptophan low, the operon is transcribed; the resulting mRNA is translated to produce a full set of biosynthetic enzymes, which work in tandem to synthesize tryptophan from much simpler molecules. Tryptophan high: the bacterium shuts down production of the enzymes, which are no longer needed. Repressors Turn Genes Off and Activators Turn Them On Within the operon’s promoter is a cis-regulatory sequence that is recognized by a transcription regulator. When this regulator binds to this sequence, it blocks access of RNA polymerase to the promoter, thereby preventing transcription of the operon (No production of the tryptophan-producing enzymes). The transcription regulator is known as the tryptophan repressor, and its cis-regulatory sequence is called the tryptophan operator. These components are controlled in a simple way: the repressor can bind to DNA only if it has also b.ound several molecules of tryptophan Both an Activator and a Repressor Control the Lac Operon The Lac operon encodes proteins required to import and digest the disaccharide lactose, a key nutrient in milk. In the absence of glucose, the bacterium makes cAMP, which activates CAP to switch-on genes that allow the cell to utilize alternative sources of carbon—including lactose. The Lac repressor shuts off the operon in the absence of lactose. This arrangement enables the control region of the Lac operon to integrate two different signals, so that the operon is highly expressed only when two conditions are met: glucose must be absent and lactose must be present. DNA Looping Can Occur During Bacterial Gene Regulation Complex Switches Control Gene Transcription in Eukaryotes A Eukaryotic Gene Control Region Includes Many cis-Regulatory Sequences DNA looping allows transcription regulators bound at many positions to “communicate” with the proteins that assemble at the promoter. Many transcription regulators act through Mediator, while some interact with the general transcription factors and RNA polymerase directly. Eukaryotic Transcription Regulators Work in Groups An individual transcription regulator can often participate in more than one type of regulatory complex. Individual eukaryotic transcription regulators function as regulatory parts that are used to build complexes whose function depends on the final assembly of all of the individual components. Each eukaryotic gene is therefore regulated by a “committee” of proteins, all of which must be present to express the gene at its proper level. In solution; the protein–protein interactions between transcription regulators and between regulators and coactivators are too weak for them to assemble In very large and complex gene control regions; this assembly may be accompanied by a phase transition to form a biomolecular condensate, whereby all the components are held together even more efficiently by keeping them in rough proximity even when individual proteins disassociate from DNA. Some Transcription Activators Work by Releasing Paused RNA Polymerase Eukaryotic Transcription Repressors Can Inhibit Transcription in Several Ways