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29 Cards in this Set
- Front
- Back
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What is the relation of gene expression profiles and cancer? |
1. Cancer is disease of gene misregulation.
2. Stepwise heritable decisions of expression misregulation lead to proliferation. 3. Specific inheritance pattern= specific targets |
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What are the major points of Gene expression regulation? |
1. Transcription: Initiation, Elongation 2. Postranscriptional: Processing, Localization, Stability 3. Translation: Initiation/Frequency 4. Post-translational: Localization, Stability, Regulation of Protein Activity. |
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What is the template strand, coding strand, and basics of transcription? |
Template: DNA strand that acts as a template for the mRNA transcript. Coding: DNA strand with identicle sequence to transcript except T and U substitute. Basic transcription: mRNA produced by RNA polymerase activity in a 5' to 3' direction adding new nucleotides at the 3' end. |
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How, when, and where does transcription know where to start? |
1. Promoter Regions: Regulatory Sequence (95%) and DNA Binding Proteins (5%). 2. Enhancer/Silencer Regions: Activator and Repressor Binding Sites ***Regulation involves access of proteins to a DNA binding site. |
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What is the basic idea of regulation for transcription shown by the Lac Operon? |
1. Recognize DNA Sequence 2. Block Access 3. Only Unblock under Certain Conditions. |
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What is the length of a DNA sequence needed to form a single unique sequence in the 6 billion base pair genome? |
16 base pairs. We use this method for 95% of transcripts |
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What are DNA binding proteins and how are they involved in transcription regulation? |
1. Small proteins which bind 4 to 8 bp recognition sites on DNA. 2. Promoters have high concentration of recognition sites for DNA BPs which sense one another via molecular interactions. 3. Once proper proteins are in place, co-activators and repressors determine transcription. |
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How do Pol I, II, and III differ in promoter type, transcript type, and Fraction of transcripts in the cell? |
*Pol II transcripts give cells their personality. |
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What are co-activators and co-repressors, and how do they regulate transcription? |
Co's are recruited by DNA binding proteins. Multiple factors cooperate to increase or decrease polymerase recruitment. |
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What is Max, and why is it a unique molecule? |
1. Max is both a repressor and activator depending on whether it is paired with c-Myc or Mad. c-Myc + Max = Activator Mad + Max= Repressor *c-Myc is a transcription factor that is related to an oncogene and cancer. |
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How is transcription of various globin genes determined? |
ß-Globin variants are expressed in a temporal program using one enhancer. Loops are formed depending on which gene promoter DNA binding proteins are available for transcription. |
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What may occur if gamma globin gene promoters have a mutation which disturbs a specific transcription factor? Explain. |
If the transcription factor was associated with a co-repressor then loss of repression would lead to persistence of fetal hemoglobin. *ß-Thalassemias may occur if a ß promoter mutation effects only one of the many transcription factor binding sites. |
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A mutation in a DNA binding protein site in the gamma globin gene causes persistent expression of gamma globin in adults. What is the site likely to be and Why? |
1. Involved in repressing transcription. If a repressor for gamma globin fails in an adult, then we get transcription of the globin gene. Therefore the site must have been involved in repression of transcription. |
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ß-Thalassemias are associated with decreased hemoglobin, but some hemoglobin is still made. Mutations causing these diseases are most likely to be what type and why? |
1. Promoter mutations. If some is made then there are working and non-working promoters to create transcripts. |
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How is chromatin involved in inhibition of transcription? |
1. If you do not have access to the DNA you cannot transcribe it. 2. DNA bound to histones is much greater affinity than transcription factors and other proteins. *Major mechanism for inhibiting transcription |
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How is DNA accessed or bound in histones? |
1. N-terminal tails of histones can be covalently modified. This affects DNA binding and different modifications will allow access to various parts. |
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What is the most important post-translational modification of histones that is likely to disrupt DNA contact? |
1. Acetylation of Lysine. ***Histone acetylation correlates with increased transcription. |
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How can long non-coding RNA (lncRNA) like Xist affect gene expression? |
1. They bind and recognize DNA sequences 2. Recruit and activate/inhibit DNA modifying enzymes 3. Recruit and Activate/inhibit histone modifying enzymes. |
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What are writers, readers, and erasers, and how do they relate to histone modifications and transcriptional regulation? |
1. Writers: Enzymes that add covalent mods to histones. 2. Readers: Protein domains that bind mods and impact chromatin structure or transcription 3. Erasers: Enzymes that remove covalent histone mods. |
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What is the histone code hypothesis? |
1. Proposition that combinations of post-translational mods on histones encode info beyond the meaning of each individual mark. 2. Mods don't necessarily alter physical behavior buth they change ability to recruit other factors that alter chromatin properties. |
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What is the rule to summarize a complex regulatory pathway of inhibition and activation? |
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What is Zolinza (Vorinostat) and what does it do? |
1. HDAC Inhibitor: Histone deacetylase inhibitor- Prevents the removal of acetyl groups increasing transcription 2. Used in treatment of cutaneous lymphoma |
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What is an HDAC Inhibitor and how does it work? |
Ultimately activates transcription of tumor suppressor gene inhibiting cancer growth. |
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Which of the following pathways indicates inhibition overall? Explain. |
B represents inhibition because it is the only pathway with an odd number of inhibitory arrows. |
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What is the relationship between transcriptional control and cell fates? Explain. |
1. Development of distinct cell fates requires making and inheriting/remembering decisions 2. Specific transcription factors can contribute to cell fate. 3. Cell identity can be changed or returned to an earlier progenitor by altering transcription. |
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How are fate decision made? What are PU.1 and GATA-1 and how are they involved? |
1. Fate decisions are made by competition between transcription programs. The factor that wins the tug of war is remembered and inherited. PU.1= Favors Myeloid Progenitors GATA-1= Favors Erythroid Progenitors Cytokines influence tug of war for these early progenitors |
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How is DNA methylation involved in transcriptional control? |
1. Bases such as cytosine can be methylated. 2. Methylation blocks or recruits certain proteins and factors which influence transcription. *DNA Methyltransferases recruit HDACs which deacetylate and reduce transcription |
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How is DNA methylation inherited? |
1. Methylation primarily occurs in some CG sites. The complement is also CG and is methylated.
2. Replication leaves one strand each with a methylated Cytosine. 3. Maintenance Methylases see one methylated cytosine of a CG pair and methylate the C of the complementary CG pair. |
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What is Decitabine and how is it used therapeutically? |
1. Reduces overall DNA methylation reactivating some repressed genes. 2. Used to treat certain myelodysplastic syndromes. |
