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32 Cards in this Set
- Front
- Back
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Cell Differentiation
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The process by which cells become structurally and functionally different from one another
The result of changes in the pattern of gene expression Gradual Cells pass on their determined state to their progeny A fully differentiated cell reaches a terminal and stable state. |
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Cell Differentiation - signals
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can be controlled by external signals
Signals are instructive yet selective Allows the same signals to be used more than once Generally cells stop proliferating before terminally differentiating Cells rarely divide after terminal differentiation; if they do divide they pass on their differentiated state |
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Differentiated Cell Types
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Epithelial Cells
Fat cell Nerve cell RBC Olfactory neuron Retinal Red |
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Analyzing DNA Expression
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Measuring mRNA levels: Northern blot, Real-time PCR, Microarrays
Reporter gene constructs tell you where a gene is expressed |
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Control of Gene Expression
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Gene activity can be controlled at different levels
Transcription: RNA processing and transport; translation |
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Control of Transcription
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RNA polymerase II binds to the start site of transcription in the promoter region
Binding is regulated by general and tissue-specific transcriptional regulators Regulators can activate or repress transcription |
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Regulatory Regions control Gene expression
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Elastase gene normally expressed in the pancreas
Growth hormone normally expressed in the pituitary Regulatory region specifies where the gene is expressed. |
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Gene-Regulatory Proteins Bind to the Control Regions
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General transcription factors form the initiation complex
Co-activators and activators are also required to start transcription Specificity of activation due to the particular combination of gene-regulatory proteins |
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Enhancer
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regulatory region separate from the promoter
Binds activator to position it at the promoter |
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External Signals can Activate Genes
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Ras-MAPK pathway
Activated by a tyrosine kinase receptor MAPK activates transcription by phosphorylating a transcription factor |
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Steroid Hormone Signaling
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Steroids are lipid soluble and can pass through the membrane
Steroid response elements act as enhancers |
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Transcription Factors
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Can regulate The activity of more than one gene
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Maintaining a Pattern of Differentiated Gene Activity
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1) Positive Feedback Loop
2) Produce large quantities of the regulatory elements in the original cells (Drosophila Hox genes) 3) Localized structural and chemical changes to the chromatin |
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Chromatin
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The complex of DNA, histones, and other proteins that make up the chromosomes
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Heterochromatin
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Chromatin that is packaged into a structure that cannot be transcribed
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Different Responses to DNase 1
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Active genes are not packaged tightly: accessible to transcription factors and other enzymes such as the nuclease DNase1, Some active genes show a hypersensitivity to digestion by DNase1
Inactive genes are packaged tightly in heterochromatin: Not accessible to transcription factors or DNase1 |
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X-Chromosome Inactivation
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Early in mammalian development one copy of the X chromosome is inactivated in females
Inactivation occurs through the formation of heterochromatin Inactivation maintained in subsequent cell divisions |
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Chemical Modification of Chromatin: DNA Methylation
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On cytosine residues in vertebrates, Methylation correlates w/lack of transcription
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Chemical Modifications of Chromatin: Histone modifications
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Methylation, acetylation, or phosphorylation on specific residues
Acetylation correlates w/active transcription Methylation correlates w/transcriptionally silent heterochromatin |
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Chemical Modificaitons of Chromatin
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Modifications thought to exert their influence on transcription through the proteins they recruit to the altered sites
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Inheritance of Methylation Patterns
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In vertebrate DNA a large proportion of cytosine bases in CG pairs are methylated
Daughter DNA helices lack methyl groups on new strands AGter Methylation Parental pattern of DNA methylation is inherited in both daughter helices |
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hematopoiesis
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blood formation
all blood cells arise from a population of multipotent stem cells hierarchical system Early in development these cells are derived from the yoke sac and a section ofthe aorta Colonize other regions mainly the liver and the bone marrow In adults the bone marrow is the source of all blood cells The microenvironment (niche) in the marrow is made up of connective-tissue cells and the molecules they secret Wnt molecules important for stem cell self-renewal |
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Hematopoietic Factors
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These factors control cell differntiation and cell proliferation
Discovered studying blood cell differentiation in culture Not all are produced in the bone marrow Difficult to determine if specifically affecting differentiation or survival and proliferation of specific cell lineages |
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Hematopoietic Factors: growth factors
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Erythropoietin
G-CSFs GM-CSFs Interleukin-3 Stem cell factor M-CSFs |
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Globin Genes: Hemoglobin Switching
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Different hemoglobins at different times during development
Requires the coordinated regulation of two sets of globin genes (a and B) Extensive regulatory control regions |
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Globin Regulatory Control Regions
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Sites for transcription factor binding: general and cell specific
Locus control region (LCR) involved in directing the developmentally correct sequence of expression of the whole B-globin gene cluster |
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Successive Activation by the LCR
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THe LCR makes contact w/each gene in succession during development
The LCR may act by promoting the transition from transcription initiation to transcription elongation by RNA polymerase II |
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Sturcture of an Ab
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Composed of two heavy chains and two light chains
Most of the protein sequence has a "constant" structure The region that binds the Ag is "variable" HHuman immune system can produce 10^15 different Abs |
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DNA Rearrangements: VDJ Recombination
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Irreversible rearrangement of DNA provides variability
Occurs during B-lymphocyte development One cell gereates one type of Ab |
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Differentiation in the Epidermis
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Skin has three layers
Epidermis mainly consists of keratin-containing kertainocytes Keratinocyte differntiation: Fill w/keratin as they mature, Eventually form a layer of dead cells Kept in supply by stem cells in the basal layer |
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Cell Adhesion Molecules in Epidermal Cell Differentiation
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Cadherin-containing desmosomal junctions connect cells in the upper layers
Gives skin its mechanical strength Cell in the basal layer express integrins to connect to the basal lamina The stem cells express higher levels of integrins |
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Epithelial Cells in the Gut
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Structures of the epithelium in the small intestine: Villi, Crypts
Epithelial cells in the villi are continusously replaces as they are shed from the tip Stem cells near the base of the cryptes supply new epithelial cells Wnt signaling is essential for stem cell proliferation and cell differentiation |
