The repressor protein binds to the operator site and inhibits transcription. However, if lactose is present in the environment, it can bind to the repressor protein and inactivate it, effectively removing the blockade and enabling transcription of the messenger RNA needed for synthesis of these genes lower portion of the figure below. Example of Repressible Transcription: E.
These genes generally transcribe continuously since the bacterium needs tryptophan. However, if tryptophan concentrations are high, transcription is repressed turned off by binding to a repressor protein and activating it as illustrated below.
After fertilization, the cells in the developing embryo become increasingly specialized, largely by turning on some genes and turning off many others. Each type of cell has a particular pattern of expressed genes. Gene expression in eukaryotes may also be regulated through by alterations in the packing of DNA, which modulates the access of the cell's transcription enzymes e.
The illustration below shows that chromosomes have a complex structure. The DNA helix is wrapped around special proteins called histones, and this are wrapped into tight helical fibers. In addition, there are many more regulatory proteins in eukaryotes and the interactions are much more complex. In eukaryotes transcription takes place within the membrane-bound nucleus, and the initial transcript is modified before it is transported from the nucleus to the cytoplasm for translation at the ribosome s.
The exons encode the amino acid sequence for protein synthesis that is transcribed to messenger RNA. Attenuation regulates the termination of transcription as a function of tryptophan concentration.
At low levels of trp full length mRNA is made, at high levels transcription of the trp operon is prematurely halted. Attenuation works by coupling transcription to translation. Prokaryotic mRNA does not require processing and since prokaryotes have no nucleus translation of mRNA can start before transcription is complete. Consequently regulation of gene expression via attenuation is unique to prokaryotes.
Attenuation is mediated by the formation of one of two possible stem-loop structures in a 5' segment of the trp operon in the mRNA. If tryptophan concentrations are low then translation of the leader peptide is slow and transcription of the trp operon outpaces translation. This results in the formation of a nonterminating stem-loop structure between regions 2 and 3 in the 5' segment of the mRNA. Transcription of the trp operon is then completed. If tryptophan concentrations are high the ribosome quickly translates the mRNA leader peptide.
Because translation is occurring rapidly the ribosome covers region 2 so that it can not attach to region 3. Consequently the formation of a stem-loop structure between regions 3 and 4 occurs and transcription is terminated.
Regulation of Gene Expression in Eukaryotes. The genetic information of a human cell is a thousand fold greater than that of a prokaryotic cell.
Things are further complicated by the number of cell types and the fact that each cell type must express a particular subset of genes at different points in an organisms development. Regulating gene expression so that a particular subset of genes is expressed in a specific tissue at specific points of development is very complicated. This increased complexity in regulation lends itself to malfunctions that cause disease. Three ways that eukaryotes regulate gene expression will be discussed: alteration of gene content or position, transcriptional regulation and alternative RNA processing.
Alteration of Gene Content or Position. The copy number of a gene or its location on the chromosome can greatly effect its level of expression. Gene content or location can be altered by gene amplification, diminution or rearrangement.
Gene Amplification. The expression of a particular gene can be augmented by amplifying its copy number. Histone proteins and rRNA are needed in large quantities by almost all eukaryotic cells therefore the genes encoding histones and rRNA exist in a permanently amplified state.
Gene amplification can present problems with the use of chemotherapeutic drugs. Methotrexate inhibits dihydrofolate reductase, the enzyme responsible for regenerating the folates used in nucleotide synthesis. Tumor cells often become resistant to the drug because the gene encoding dihydrofolate reductase is amplified by several hundred fold resulting in more enzyme production then the drug can handle.
Gene Diminution. A gene whose expression is only needed at a particular developmental point or in a particular tissue may be shut off by gene diminution. As reticulocytes mature into red blood cells all of their genes are lost as the nucleus is degraded. Gene Rearrangements. Gene rearrangement is used to generate each of the genes encoding the millions of different antibodies that are produced by B cells.
Sometimes bad gene rearrangements occur that lead to improper gene regulation. This frequently occurs in cancer cells. Translocation of a segment from chromosome 8 to chromosomes that encode immunoglobulins leads to activation of a gene that transforms healthy B cells into Burkitt's lymphoma cells unregulated proliferating B cells.
Transcriptional Regulation. Through Chromosomal Packaging. Regions of each of the different chromosomes are either packaged as heterochromatin or euchromatin. In heterochromatin the DNA is very tightly condensed and rendered inaccessible to the transcriptional machinery, consequently heterochromatin is transcriptionally inactive. In human females one of each of the two X chromosomes is completely inactivated by being packaged into a heterochromatin to form a Barr body.
The Cys residues in DNA in the heterochromatin are heavily methylated suggesting that methylation may play a role in the maintenance of heterochromatin. Drugs that interfere with methylation cause activation of previously inactive genes found in heterochromatin.
In euchromatin the DNA is not as condensed and is accessible to the transcription machinery. The regions of a chromosome that are maintained as hetero- and eu- chromatin may vary in a cell specific manner.
This may enable the cells of specific tissues to express a particular subset of genes required for tissue function.
Through Individual Genes. Trans-acting Elements. Proteins that participate in regulating gene expression are often called trans acting elements.
At least different proteins, many specific for the regulation of a particular gene, are known. Others play a more general role in regulating gene expression in a manner analogous to the activation of numerous prokaryotic genes by the CAP-cAMP complex. Trans-acting factors have multiple domains required for activity and may include DNA-binding, transcription-activating and ligand-binding domains.
DNA Binding Domains. The DNA-binding domains of a regulatory protein generally consist of one of three motifs: helix-turn-helix, zinc finger or leucine zipper. DNA-binding proteins possessing these motifs bind with high affinity to their recognition sites and with low affinity to other DNA.
A very small portion of the protein makes contact with the DNA through H-bonds and van der Waals interactions between amino acid side chains and the functional groups in the major groove and the phosphate backbone of the DNA. The remainder of the protein is involved in proper positioning of the DNA-binding domain and in making protein-protein contacts with other transcriptional proteins. The Helix-Turn-Helix Motif. This page appears in the following eBook. Aa Aa Aa. Promoters and proteins.
How do prokaryotes regulate gene expression? Turning genes on. Turning genes off. Turning genes up or down. How do eukaryotes regulate gene expression? Control at the DNA level. Figure 1: Eukaryotic cells must tightly fold their DNA so that it fits within the cellular nucleus. Control at the transcription level.
Control via RNA splicing. More on gene expression. Can the central dogma be reversed? How can the environment affect gene expression? How does eukaryotic DNA unfold and open? How, exactly, does RNA splicing occur? Control via RNA stability. Control at the translation level. Key Questions What else is there to know about operons?
How do environmental influences affect gene expression? What role does noncoding RNA play in gene expression? How do genes express and regulate themselves? Key Concepts intron exon splicing transcription factor. Topic rooms within Genetics Close. No topic rooms are there. Browse Visually. Other Topic Rooms Genetics.
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