Organization and regulation Flashcards
What was the triumph of classical biochemistry
To show that isolated components of cells could retain their individual activities after being purified. But within the cell these functions must be integrated and regulated. There are 2 main cellular networks: a network of metabolic pathways that governs the possible interconversions of metabolites and a parallel network of regulatory interactions that control the traffic through these pathways. For instance, feedback inhibition may act to shut off a pathway, if the end product is present in adequate concentration.
Explain a little bit about the two networks
Each network(metabolic and regulatory)has both static and dynamic features. There is a clear logical distinction between the two networks, but not so clear physical distinction- signaling molecules may be metabolites. In feedback inhibition, a molecule participates in both metabolic and control networks.
Explain the how protein activity is regulated
Cells overlook no opportunity to exert control. The central dogma- DNA to mRNA to protein suggests several possible leverage points for regulation of protein activity. The mechanisms that are applied at the levels of expressed proteins have faster effects than those that control gene expression.
Why do we say that transcription and translation are dynamic
They must be dynamic to produce the right amount of protein at the right time the right place. In this way, the cells can respond to stimuli by altering their physiological state or their physical form. Therefore, living things must regulate the synthesis of proteins encoded in their genomes.
What are the driving forces of these changes in profiles of protein expression
It may be changes in the environment(external), internal signals directing different stages of the cell cycle or developmental programmes (internal).
Give an example that displays how transcription and translation is dynamic
The appearance of lactose in the medium can trigger transcription of the lactose operon in E.coli. Transcription of another operon, encoding enzymes for the biosynthesis of the amino acid tryptophan is present in adequate concentrations. Similarly, a human cell may differentiate into a neuron, sprouting dendrites and an axon, and express tissue-specific or even cell-specific proteins.
Describe transcriptional regulation in prokaryotes
A specific focus of transcriptional regulation is at or near the binding site of RNA polymerases to DNA, just upstream of the beginning of the gene(5’). Repressors can turn off transcription by binding the the binding site and blocking polymerase activity. Promoters can actively recruit polymerases through cooperative binding along with the polymerase to the a site on the DNA.
Describe transcriptional regulation in eukaryotes
It is more complex. Transcriptional regulators bind to sites near the gene and also at remote sites. The control of human beta-globin illustrates this. Regulatory interactions also govern the expression of other transcription factors. Eukaryotic control networks show greater complexity in their logics and dynamics than those of viruses or prokaryotes. Other mechanisms of transcription regulation involved changes in patterns of methylation of DNA associated with changes in the structure of chromatin. In differentiation, DNA methylation is a mechanism that survives cell division. Methylation of cytosine in CpG islands silences the adjacent genes possibly stimulating chromatin remodeling. When a cell divides, enzymes copy the methylation patterns, preserving the settings of the regulatory switches.
Explain what is meant by the gift of complexity
The gift of complexity is robustness. Eukaryotic networks show an ability to reprogramme themselves to respond to stimuli by changing cell state. The source of robustness appears to be redundancy. Yeast has about 6000 genes. Under normal conditions about 80% are expressed. It is also true that yeast can survive about 80% of single-gene knockouts- this means that many of these genes are redundant and redundancy provides robustness.
Explain the control of the beta-globin gene expression
The protein-coding genes of the globin loci interact with many control regions. The beta-globin region includes promoters near to individual genes, a locus control region upstream of the most 5’ gene, a 250bp pyrimidine rich region 5’ to the sigma gene and enhancer regions which may appear on the same chromosome, in some cases near to and in other distant from the gene they control, or on different chromosomes.
Control of beta-globin gene expression is asserted for both tissue specificity and developmental progression. A well known enhancer of globin expression erythropoietin, a glycoprotein hormone located on chromosome 7. Erythropoietin works indirectly by binding to a receptor to activate intracellular signaling pathways. Erythropoietin is sensitive to to oxygen tension. Hypoxia increases erythropoietin production- at high altitude. Acetylcholinesterase is known for its physiological role in neural synapses and neuromuscular junctions. It also regulates globin synthesis in muscles.
Explain how mammalian females are X-chromosome-silenced mosaics
An example of gene silencing by DNA methylation is the formation of Barr bodies in female placental mammals. Cells of mammalian females(except for oocytes) have 2 X chromosomes. The product of the Xist gene(X-inactive specific transcript) on one of the X chromosomes inactivates that entire chromosome and it causes it to form a compact, transcriptionally inert object, called a Barr body. Expression of the Xist gene on the other X chromosome is suppressed by cytocine methylation of its promoter, leaving that chromosome normal in function and structure. As a result males and females have one active X chromosome. This is the mammalian solution of the “dosage compensation” problem that arises because the genomes of males and females contain different numbers of copies of the X chromosome genes.
How do the cells of mammalian females choose which X chromosome to inactivate
Each cell chooses at random, this is why most mammalian females are mosaics of cells expressing genes from alternative X chromosomes. A visable example of this mosiacity is a calico cat, a female. A calico cat has an orange coat allele on the X chromosome inherited from one parents and a black coat allele on the other X chromosome inherited from the other parent. In the white patches of the coat neither allele is expressed. The genotype can be seen from the phenotype. The size of the patches on the coat reveals when the genes were inactivated. In female marsupials all cells inactivate the paternal X chromosome- this is genomic imprinting(the dependence of phenotype on the parental origin of the gene)
