When is lac operon on

A major type of gene regulation that occurs in prokaryotic cells utilizes and occurs through inducible operons. Inducible operons have proteins that can bind to either activate or repress transcription depending on the local environment and the needs of the cell.

The lac operon is a typical inducible operon. As mentioned previously, E. One such sugar source is lactose. The lac operon encodes the genes necessary to acquire and process the lactose from the local environment, which includes the structural genes lacZ, lacY, and lacA.

Only lacZ and lacY appear to be necessary for lactose catabolism. CAP binds to the operator sequence upstream of the promoter that initiates transcription of the lac operon. However, for the lac operon to be activated, two conditions must be met. First, the level of glucose must be very low or non-existent. 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. Proteins with this motif form symmetric dimers that recognize a symmetric palindromic DNA sequence. Each monomer of the dimer contains a region in which two a helices are held at 90 degrees to each other by a turn of four amino acids. One set of helices makes contact with about five base pairs in the major groove.

The other set sits atop the phosphate backbone and helps to properly position the set of helices that fits into the major groove. Therefore, the operon will not be transcribed when the operator is occupied by a repressor.

Besides its ability to bind to specific DNA sequences at the operator, another important property of the lacI protein is its ability to bind to lactose. When lactose is bound to lacI , the shape of the protein changes in a way that prevents it from binding to the operator. Therefore, in the presence of lactose, RNA polymerase is able to bind to the promoter and transcribe the lac operon, leading to a moderate level of expression of the lacZ , lacY , and lacA genes.

Proteins such as lacI that change their shape and functional properties after binding to a ligand are said to be regulated through an allosteric mechanism. CAP is another example of an allosterically regulated trans -factor. CBS is located very close to the promoter P. Thus, the presence of cAMP ultimately leads to a further increase in lac operon transcription. The physiological significance of regulation by cAMP becomes more obvious in the context of the following information.

The concentration of cAMP is inversely proportional to the abundance of glucose: when glucose concentrations are low, an enzyme called adenylate cyclase is able to produce cAMP from ATP.