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Tuesday, May 23, 2017 Title: Transcription and gene expression Learning Objectives: HL only We are learning…. • How do proteins regulate gene expression? • How does the environment of a cell and an organism impact gene expression? • How are nucleosomes involved in the regulation of gene expression? • What is splicing? Keywords: Starter Describe the process of transcription • • • • • Splicing Promotor Enhancer Silencer Promoter-proximal elements Gene expression – an introduction All cells have the same genes. Every cell in the body is therefore capable of making everything that the body can produce. A cell in the lining the small intestine has the gene coding for insulin just as a Beta cell lining the pancreas has a gene coding for maltase. So why do the cells of the small intestine produce maltase rather than insulin? Why do the Beta cells of the pancreas produce insulin rather than maltase? The answer is that, although all cells contain all genes, only certain genes are expressed (switched on) in any one cell at any time. So what is gene expression? Gene expression is the process by which the genetic code - the nucleotide sequence - of a gene is used to direct protein synthesis and produce the structures of the cell. Genes that code for amino acid sequences are known as 'structural genes'. The process of gene expression involves two main stages: Transcription: the production of messenger RNA (mRNA) by the enzyme RNA polymerase, and the processing of the resulting mRNA molecule. Translation: the use of mRNA to direct protein synthesis, and the subsequent post-translational processing of the protein molecule. A structural gene involves a number of different components: Exons code for amino acids and collectively determine the amino acid sequence of the protein product. It is these portions of the gene that are represented in final mature mRNA molecule. Introns are portions of the gene that do not code for amino acids, and are removed (spliced) from the mRNA molecule before translation. Gene control regions Start site. A start site for transcription. A promoter. A region a few hundred nucleotides 'upstream' of the gene (toward the 5' end). It is not transcribed into mRNA, but plays a role in controlling the transcription of the gene. Transcription factors bind to specific nucleotide sequences in the promoter region and assist in the binding of RNA polymerases. Enhancers. Some transcription factors (called activators) bind to regions called 'enhancers' that increase the rate of transcription. These sites may be thousands of nucleotides from the coding sequences or within an intron (some enhancers are conditional and only work in the presence of other factors as well as transcription factors). Silencers. Some transcription factors (called repressors) bind to regions called 'silencers' that depress the rate of transcription. What are transcription factors? Transcription factors are proteins which bind to specific DNA sequences, thereby controlling the transcription of DNA to mRNA. These transcription factors bind to a gene’s promoter region (the part where transcription begins). Try and explain the diagram below. Transcription factor (protein) produced after transcription/translation Factor binds to DNA – promotes transcription. Some genes are expressed (switched on) Proteins produced Gene expression in haemoglobin Haemoglobin is made up of four polypeptide chains. Each is known as a globulin. In adult humans, two of the polypeptides are alpha-globulin and two are beta-globulin. However, in a human fetus, the haemoglobin is different, with much of the betaglobulin being replaced by a third type: gamma-globulin. Fetal haemoglobin has a higher affinity for oxygen than adult haemoglobin, meaning it can become saturated with oxygen more easily where there is little oxygen available. Humans have genes that code for the production of all three types of globulin. The production of the different haemoglobins depends upon which gene is expressed. The expression of these genes changes at different times during development. The impact of the environment on gene expression Neither genes nor environment dominates development; rather there is continual interaction between genes and the environment, with both contributing to the phenotype. However, studies of twins have been used to determine the relative effects of genetic and environmental factors on the development of a type of diabetes. Try the exam questions (Q2) Genetic variation and heritability Heritability can be defined as the proportion of all phenotypic variation (phenotype - visible characteristics) in a population that is due to genetic effects. Basically the amount of characteristics an organism has which are due to the genes it has inherited. Exam grades 'more nature than nurture' How could you test this hypothesis? IQ – Nature vs nurture Individuals who share the same genes, such as twins, also share similar mental abilities. Monozygotic (identical) twins raised separately are highly similar in IQ (0.86), more so than dizygotic (fraternal) twins raised together (0.6) and much more than adoptive siblings (~0.0). In general, identical twins who were raised in different homes have scores similar enough that many estimate that between 50% and 75% of intelligence scores differences are related to genetic variation (Bouchard, 1996; Devlin et al., 1997; Neisser et al., 1996; Plomin, 2003). What implications might this research have for education policy? Try the exam questions (Q1) Environmental factors can affect gene expression, such as the production of skin pigmentation during exposure to sunlight in humans. How do organs develop in their proper positions? How do cells "know" where they are within a developing organism? Morphogens are chemicals found in the developing embryo. They are distributed unevenly and different concentrations of morphogens affect gene expression. This leads to embryonic cells developing differently, and eventually taking on a specific function – known as cell specialisation or differentiation. How do nucleosomes regulate transcription? Nucleosomes consist of DNA wrapped around eight histone proteins and held together by another histone protein. Histone tails have specific functions. Acetyl, methyl phosphate or groups can be added to the tails of histones. By adding groups to the tail of histones the DNA either becomes more condensed (more tightly coiled – inhibits transcription) or less condensed (less tightly coiled – promotes transcription). Chemical modification of histone tails can either activate or deactivate genes by condensing or relaxing DNA coils and making genes less or more accessible to transcription factors. Transcription of DNA strand begins starts at a special nucleotide sequence called a promoter. This promoter is located near to the beginning of a gene. This is where RNA polymerase (the enzyme which catalyses transcription of DNA by attaching to DNA) begins attaching nucleotides to one another. Transcription ends at another special nucleotide sequence called a terminator. This is the point at which RNA polymerase detaches from the transcribed RNA molecule and DNA. Introns – do not code for protein Exons – do code for proteins Pre-mRNA The non-coding introns need to be removed from premRNA before it leaves the nucleus….. Splicing The introns are removed from pre-mRNA by small nuclear ribonucleoproteins (snRNP’s). Together with proteins they form a complex known as a spliceosome. These complexes cut out the introns and splice together the exons. The result is a functional mRNA molecule that passes through a pore in the nuclear envelope to reach the cytoplasm, where translation takes place.