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Lecture 16

Lecture 16: "Epigenetics"

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Biology 1002B
Tom Haffie

Biology Lecture No. 16: Epigenetics th Wednesday March 7 , 2012 RECALL: -Poly A polymerase, ribosomal RNA and transfer RNA must pass through a nuclear pore in order to get from where it is they are synthesized to where they function. -Proteins are targeted to the Rough ER, and then transported into secretory vesicles to the Golgi apparatus. Some of these are then exported outside the cell. At the same time, endocytic vesicles are imported into the cell and fuse with the lysosomes, which break down endocytic food particles. -Lysosomes can also be of use in digesting old mitochondria. So any enzymes that need to end up in the lysosomes need to be targeted appropriately for the Rough ER. -The synthesis of membrane proteins is targeted to the ER by a peptide tag that is first to emerge from the ribosome. However, this tag can only be found in the coding region where the final protein receives its function. Micro RNA & Their Significance: -Micro RNA (miRNA) is transcribed from genes in the nucleus just as all RNA molecules. Like most RNA molecules, it leaves the nucleus, complementary base-pairs with itself (two strands result), and is associated with a protein. -In the case of miRNA, this protein is called dicer whose function is to chop up miRNA into smaller pieces. This then attracts the attention of more proteins which degrade it down to a single strand. -This process finalizes miRNA’s function, which can only be achieved through a single strand. The function of miRNA in this state is to complementary base-pair with specific mRNAs and in doing so inhibit their translation in the cytoplasm. -This is a prime example of translational control. miRNAs are very widespread and important in gene regulation. The Proteasome & Post-Translational Regulation: -In the instance that a cell doesn’t want a protein or a particular enzyme’s activity, proteins are recycled in the organelle known as the proteasome. -The process begins with proteins entering the proteasome, becoming degraded, and released into bits of peptides that are degraded to amino acids by cytosolic enzymes. -Ubiquitin is a short protein that is used to tag proteins for recycling in the proteasome where it is degraded. One can regulate the expression of proteins by regulating their recycling and how easily they are degraded. Protein Function & Post-Translational Control: -After a protein is made, what is done to impart its intended function post-translation? Similar to apoproteins that require a cofactor, it is sometimes necessary to cut sections of proteins. -Regulation of protein expression can also be achieved by the binding of molecules as in phosphorylation where kinase enzymes add phosphate groups to peptides. Epigenetics: -Epigenetics refers to the stable change in gene expression, not their sequence. This phenomenon does not fit in with the “Transcription-Translation” model. -Epigenetic changes do not involve mutations as they are only considered with affecting genes and their expression. This effect is stable over the organism’s life span and/or from one generation to the next. Gene Silencing & DNA Methylation: -One primary example of the effects of epigenetics is observed in the coat colours of mice, where the normal phenotype is agouti as opposed to a yellow colour of coat. The agouti genotype is expressed only in the skin. -Yellow mice have a special allele of the agouti genotype which is expressed everywhere and is the main reason they are yellow as well as obese and full of tumours. -The allele for a yellow coat in mice is dominant (present in heterozygotes) and is made possible due to the presence of IAP, a mobile element similar to transposons. -IAP contains very powerful expression sequences (promoter and enhancer) that when inserted next to the agouti gene, drives expression of that gene everywhere in the mouse, all the time. -It is possible to inhibit this powerful promoter sequence by placing methyl groups on DNA by a process called cytosine methylation. Modifying the expression of a gene by methylating its promoter renders a normal allele. Cytosine Methylation & The Role Of Epigenetics: -In yellow mice mothers, most babies born will be yellow as IAP is demethylated, a process not due to Mendelian genetics. The methylation state of the mother influences the methylation state of the babies. -By simply feeding the mother methyl groups, you can methylate the babies and hence they are born with a more normal, agouti coat. This change in diet influences the mother’s methylation state and therefore the babies’
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