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If induction tells cells what to do How do they remember these instructions for a lifetime??
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Cloning: The ultimate Transplant experiment Dolly
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Cloning: The ultimate Transplant experiment Oops-- Here’s the real Dolly (guess which tissue she was cloned from!)
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Cloning: The ultimate Transplant experiment
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So HOW does cloning work?
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Blastula stage cells Can be easily re-programmed
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But cloning success drops dramatically as the age of the nuclear donor increases Gilbert Fig. 4.6
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But cloning success drops dramatically as the age of the nuclear donor increases Gilbert Fig. 4.6 Why??
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All cells have the same DNA and thus the same library of genes yet different mRNAs are made by different cells
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Methylation is HERITABLE at the cell level and thus could be used by cells to remember decisions they have made ECB 3e 8-22
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DNA imprinting: an example of how DNA methylation influences gene expression during development
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Two maternal genomes: “normal” embryo, Poor development of Extraembryonic tissue Two paternal genomes: Very small embryo, “normal” development of Extraembryonic tissue
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Imprinting results From pre-programmed Differences in DNA methylation Of selected genes in the sperm and egg
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The DNA within cells is NOT naked!
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Instead it is wrapped around histone proteins as chromatin
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Post-translational modification of histones plays a key role in regulating gene expression
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Post-translational modification of histones plays a key role in regulating gene expression
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To understand a third mechanism of large scale gene regulation, let’s return to this experiment
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If one transferred chromatin from a de-methylated fat cell that had become a myoblast it could tranform untreated fat cells. However frequency suggests Only one or a few of the genes have this ability
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They ultimately identified a single gene- myoD - whose expression could convert,any other cell types into muscle cells
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MyoD is induced by treatments that induce mesoderm
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MyoD is expressed at the right place and time to be a master regulator of muscle development
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But is this true???
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Is myoD necessary for muscle formation? Oliver Smithies UNC Gene knockout Mario Capecchi Martin Evans Nobel prize in physiology and medicine 2007
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MyoD works with related transcription factors to regulate the muscle cell fate
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MyoD works with related transcription factors to regulate the muscle cell fate
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I can tell you and even better story
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How to Remember a Developmental Decision
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Remember that Wingless is expressed by specific cells within each segment
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Anterior Posterior Wg En Engrailed is expressed by cells posterior to those that express Wingless
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Here’s the real thing
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Engrailed expression initially requires Wingless signaling by the neighboring cells
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Later, however, Engrailed becomes autoregulatory i.e., it turns on its own synthesis
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In cells where engrailed is turned off, a set of special chromatin proteins bind to it and wrap it up in a permanently inactive state.
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We also regulate stem cells And are mutated in cancer
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We also regulate stem cells And are mutated in cancer
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