lecture 24 W11 - Lecture 24 Eukaryotic gene regulation II...

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Today’s topics 1) Cover DNA methylation and epigenetic regulation 2) Post-transcriptional regulation - alternative splicing, miRNAs, siRNAs and translational control 3) Post-translational regulation Lecture 24 (3/14/11) - Eukaryotic gene regulation II
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Molecules; Chemical bonds; Free energy Lipids Amino acids nucleotides carbohydrates membranes proteins Membrane transport Membrane proteins cytoskeleton enzymes DNA RNA Metabolism Sugar transport Electrolyte transport Kidney Nerve cells Transporters and pumps Receptors Cell-cell communication Chemical signaling development Replication transcription translation Glycolysis Fermentation Krebs cycle Photo- Synthesis & Calvin cycle Cell cycle Regulation of transcription biotechnology genomics Microbes Biology 172 flowchart (lecture 24) cancer epigenetics
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DNA methylation can lead to long-term transcriptional repression = gene silencing In most plant, animal and fungal cells, some of the cytosine nucleotides in DNA are modified by covalent addition of a methyl group Methylation of DNA blocks gene transcription Patterns of methylation are stable through successive cell divisions Necessary for proper development methyl-CpG (*CpG) are the most common sites (C next to G in linear sequence)
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Role of DNA Methylation in Development and disease Tissue-specific gene regulation associated with cell differentiation. Changes in DNA methylation can cause inappropriate activation or silencing of genes in cancer cells. X-chromosome inactivation in some eukaryotes, e.g., in mammals one of the two X-chromosomes in females is silenced to equalize the amount of gene product with males. One of the mammalian X chromosomes in females is highly methylated. Genomic imprinting is the process where methylated genes inherited from the mother or father are never expressed in the offspring. Genetically, imprinted loci behave monoallelically (the genotype of the imprinted gene doesn’t matter).
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DNA methylation (and perhaps some types of histone modifications) are “remembered” following multiple cell divisions TF DNA methyl transferase cell division “Hit and run” mechanism Before cell division Methylated DNA
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replication DNA methyltransferase recognizes The hemi-methylated strands and Methylates the other strand Other proteins will bind to The methylated DNA to affect Transcriptional silencing, but the methylation Is what allows the silencing to be remembered From one cell cycle to the next Piggy back model - Methylated strand of DNA provides a marker on the newly replicated duplex for methylation of the other strand. The methylation status of genes from the previous cell generation is remembered. Hemi-methylated
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lecture 24 W11 - Lecture 24 Eukaryotic gene regulation II...

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