It mediates many hormonal responses, controlling both gene activity and enzyme activity. The cAMP produced then binds to a protein kinase, the first of several in a phosphorylation cascade. Signal transduction mediated by cAMP is summarized in the illustration below. A different kind of signal transduction involves a hormone receptor that is itself the protein kinase. The role of enzyme-linked hormone receptors in signal transduction is summarized below.
Binding of the signal protein e. We look at signal transduction in more detail in another chapter. Consider again the illustration of the different levels of chromatin structure below. Transcription factors bind specific DNA sequences by detecting them through the grooves mainly the major groove in the double helix. The drawing above reminds us however, that unlike the nearly naked DNA of bacteria, eukaryotic nuclear DNA is coated with proteins that, in aggregate are by mass, greater than the mass of DNA that they cover.
The protein-DNA complex of the genome is of course, chromatin. Again, as a reminder, DNA coated with histone proteins forms the 9 nm diameter beads-on-a-string structure in which the beads are the nucleosomes. The association of specific non-histone proteins causes the nucleosomes to fold over on themselves to form the 30 nm solenoid. As we saw earlier, it is possible to selectively extract chromatin. Take a second look at the results of typical extractions of chromatin from isolated nuclei below.
Further accretion of non-histone proteins leads to more folding and the formation of euchromatin and heterochromatin characteristic of non-dividing cells.
In dividing cells, the chromatin further condenses to form the chromosomes that separate during either mitosis or meiosis. Recall that biochemical analysis of the 10 nm filament extract revealed that the DNA wraps around histone protein octamers, the nucleosomes or beads in this beads-on-astring structure.
Histone proteins are highly conserved in the eukaryotic evolution they are not found in prokaryotes. They are also very basic many lysine and arginine residues and therefore very positively charged. This explains why they are able to arrange themselves uniformly along DNA, binding to the negatively charged phosphodiester backbone of DNA in the double helix. Since the DNA in euchromatin is less tightly packed than it is in heterochromatin, perhaps active genes are to be found in euchromatin and not in heterochromatin.
Experiments in which total nuclear chromatin extracts were isolated and treated with the enzyme deoxyribonuclease DNAse revealed that the DNA in active genes was degraded more rapidly than non-transcribed DNA. More detail on these experiments can be found in the two links below. The results of such experiments are consistent with the suggestion that active genes are more accessible to DNAse because they are in less coiled, or less condensed chromatin.
DNA in more condensed chromatin is surrounded by more proteins, and thus is less accessible to, and protected from DNAse attack. When packed up in chromosomes during mitosis or meiosis, all genes are largely inactive.
Regulating gene transcription must occur in non-dividing cells or during the interphase of cells, where changing the shape of chromatin chromatin remodeling in order to silence some and activate other genes is possible.
Changing chromatin conformation involves chemical modification of chromatin proteins and DNA. For example, chromatin can be modified by histone acetylation, de-acetylation, methylation and phosphorylation, reactions catalyzed by histone acetyltransferases HAT enzymes , de-acetylases, methyl transferases and kinases, respectively.
For example, acetylation of lysines near the amino end of histones H2B and H4 tends to unwind nucleosomes and open the underlying DNA for transcription. De-acetylation then, promotes condensation of the chromatin in the affected regions of DNA.
Likewise, methylation of lysines or arginines the basic amino acids that characterize histones! In one case, di-methylation of a lysine in H3 can suppress transcription. These chemical modifications affect recruitment of other proteins that alter chromatin conformation and ultimately activate or block transcription. Nucleosomes themselves can be moved, slid and otherwise repositioned by complexes that hydrolyze ATP for energy to accomplish the physical shifts.
Some cancers are associated with mutations in genes for proteins involved in chromatin remodeling. This is no doubt, because failures of normal remodeling could adversely affect normal cell cycling and normal replication. Recall that X chromosomes in human female somatic cells is inactivated, visible in the nucleus as a Barr body. One of the two X chromosomes in female fruit flies is also inactivates.
However, both males and females of Drosophila presumably also us! Given the difference in X chromosome gene dosage between males and females, do males get by with fewer X chromosome gene products than females?
Experiments looking at the expression of X chromosome gene in male and female flies revealed similar levels of gene products.
In Francois Jacob, Jacques Monod, and Andre Lwoff shared the Nobel prize in medicine for their work supporting the idea that control of enzyme levels in cells is regulated by transcription of DNA. These researchers proposed that production of the enzyme is controlled by an "operon," which consists a series of related genes on the chromosome consisting of an operator, a promoter, a regulator gene, and structural genes.
The operator gene is the sequence of non-transcribable DNA that is the repressor binding site. There is also a regulator gene, which codes for the synthesis of a repressor molecule hat binds to the operator. Eukaryotic cells have similar mechanisms for control of gene expression, but they are more complex. Consider, for example, that prokaryotic cells of a given species are all the same, but most eukaryotes are multicellular organisms with many cell types, so control of gene expression is much more complicated.
Not surprisingly, gene expression in eukaryotic cells is controlled by a number of complex processes which are summarized by the following list. First, an enzyme nicknamed "Dicer" chops any double-stranded RNA it finds into pieces that are about 22 nucleotides long. This binding blocks translation of viral proteins at least partially, if not completely. The RNAi system could potentially be used to develop treatments for defective genes that cause disease.
The treatment would involve making a double-stranded RNA from the diseased gene and introducing it into cells to silence the expression of that gene. All Rights Reserved. Date last modified: February 2, Journal of Biological Chemistry , — Remenyi, A. Combinatorial control of gene expression. Nature Structural and Molecular Biology 11 , — doi Struhl, K.
Fundamentally different logic of gene regulation in eukaryotes and prokaryotes. Cell 98 , 1—4 Sproul, D. The role of chromatin structure in regulating the expression of clustered genes. Nature Reviews Genetics 6 , — doi Atavism: Embryology, Development and Evolution. Gene Interaction and Disease. Genetic Control of Aging and Life Span.
Genetic Imprinting and X Inactivation. Genetic Regulation of Cancer. Obesity, Epigenetics, and Gene Regulation. Environmental Influences on Gene Expression. Gene Expression Regulates Cell Differentiation.
Genes, Smoking, and Lung Cancer. Negative Transcription Regulation in Prokaryotes. Operons and Prokaryotic Gene Regulation. Regulation of Transcription and Gene Expression in Eukaryotes. The Role of Methylation in Gene Expression.
DNA Transcription. Reading the Genetic Code. Simultaneous Gene Transcription and Translation in Bacteria. Chromatin Remodeling and DNase 1 Sensitivity. Chromatin Remodeling in Eukaryotes. RNA Functions. Citation: Phillips, T. Nature Education 1 1 If our genes are so similar, what really makes a eukaryote different from a prokaryote, or a human from E. The answer lies in the difference in gene expression and regulation used. Aa Aa Aa. Transcriptional Regulation in Eukaryotes.
Table 1: Overview of Differences Between Prokaryotic and Eukaryotic Gene Expression and Regulation Prokaryotes Eukaryotes Structure of genome Single, generally circular genome sometimes accompanied by smaller pieces of accessory DNA, like plasmids Genome found in chromosomes; nucleosome structure limits DNA accessibility Size of genome Relatively small Relatively large Location of gene transcription and translation Coupled; no nucleoid envelope barrier because of prokaryotic cell structure Nuclear transcription and cytoplasmic translation Gene clustering Operons where genes with similar function are grouped together Operons generally not found in eukaryotes; each gene has its own promoter element and enhancer element s Default state of transcription On Off DNA structure Highly supercoiled DNA with some associated proteins Highly supercoiled chromatin associated with histones in nucleosomes.
Transcription Factors and Combinatorial Control. Figure 1: DNA footprinting reveals transcription factor specificity in different cell types.
In vivo footprinting analysis of the human beta globin promoter shows that adult erythroblasts E, lane 4 have footprints on important regulatory motifs note lighter regions, especially at CACC as compared to the other samples.
Of these cells lines, none is part of the lineage leading to red blood cells. Genomic footprinting and sequencing of human beta-globin locus: tissue specificity and cell line artifact. All rights reserved. The Role of Chromatin.
Multiple Interactions Provide Synchronous Control. References and Recommended Reading Pulverer, B. Journal of Biological Chemistry , — Remenyi, A. Cell 98 , 1—4 Sproul, D. Article History Close. Share Cancel. Revoke Cancel. Keywords Keywords for this Article.
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