Term
| Types of post-transcriptional control of eukaryotic gene regulation |
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Definition
| mRNA processing/alternative splicing, mRNA stability/degradation, translational control |
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Term
| types of transcription initiation control of eukaryotic gene regulation |
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Definition
| activation/repression by trans factors, developmental regulation, epigenetic control |
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Term
| How do cells allow for a greater variety of proteins to be made from a smaller number of genes? |
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Definition
| Alternative splicing (often in more than 2 ways) and alternative polyadenylation |
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Term
| Why do non-coding exons (occur after the stop codon) exist? |
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Definition
| Important for post-transcriptional regulation |
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Term
| How does beta-thalassemia result from alternative splicing? |
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Definition
| A mutation in intron 1 provides the splicing machinery with two splice acceptor choices – both are taken, but the “mutant” pathway is apparently preferred 9 to 1. This alternative pathway leads to a frameshift mutation, and a STOP codon is soon encountered, leading to a non-functional protein |
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Term
| Why would a protein that is involved only briefly in signaling need to have unstable mRNA? |
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Definition
| Because mRNA with a short half-life only produces a small amount of protein (reduces effective concentration) |
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Term
| How can the cell control the concentration of translated protein |
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Definition
| By controling mRNA concentration via regulated degradation of mRNA |
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Term
| How does the cell use regulated degradation of mRNA to control iron levels? |
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Definition
| At low iron, sequences in 3' end of transferring receptor mRNA binds IRE-BP to protect mRNA from degradation. At high iron levels, the protein loses its affinity for the mRNA. |
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Term
| What is RNA interference (RNAi)? |
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Definition
| RNA molecules that regulate gene expression. They can either inhibit translation or degrade mRNA based on extent of complementarity to miRNA to its mRNA target |
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Term
| Where does RNAi processing occur? |
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Definition
| Processing occurs in both the nucleus and cytoplasm. |
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Term
| How can RNAi be used in therapeutics? |
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Definition
| Can be used to down-regulate aberrantly expressed genes, such as in cancer |
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Term
| What bind to regulatory sequence elements |
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Definition
| Transcription factors (usually more than one TF per regulatory sequence element) |
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Term
| common domains of transcription factors |
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Definition
| transactivation domain (mediates i/a's between different TFs and Pol II), DNA binding domain, ligand binding domain. |
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Term
| What is the most common way TFs bind DNA? |
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Definition
| Alpha-helix sitting in the major groove of DNA |
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Term
| How can TFs achieve different DNA sequence specificities? |
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Definition
| Homo- or heterodimerization of TFs |
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Term
| In transcription, what is mediator? |
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Definition
| A commonly occurring co-activator or co-repressor (represents a non-DNA binding transcription factor complex). Acts as an intermediary beween transcription factors and the machinery |
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Term
| What is the gene organization and developmental regulation of the beta-globin locus? |
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Definition
| 5 beta-globin-like genes clustered on chromosome 11 (epsilon, G-gamma, A-gamma, psuedo-Beta, delta, Beta). mRNA transcription switches from gene to gene (from L to R) during development. As each gene is up-regulated the otehrs are down-regulated. Pseudo-beta is a nonfunctional gene. epsilon is embryonic, gamma is fetal, and beta is adult.Delta makes up 2% of adult beta-globin but its function is unclear |
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Term
| What is Hereditary Persistence of Fetal Hemoglobin (HPFH) |
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Definition
| condition where normal gamma-globin down-regulation does not occur, allowing compensation for reduced or absent beta-globin expression in beta-thalassemia. |
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Term
| What can cause Hereditary persistence of fetal hemoglobin (HPFH)? |
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Definition
| Point mutations in the gamma-globin proximal promoter region, deletions of segments of downstream globin locus DNA, sometimes encompassing part or all of the delta and beta genes. |
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Term
| What causes gamma-delta-beta-thalassemia |
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Definition
| Mutation of far upstream enhancer. The enhanceer is known as the locus control region. |
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Term
| What is the Locus Control Region (LCR)? |
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Definition
| far upstream enhancer that controls overall expression and developmental gene switching |
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Term
| What are the characteristics of epigenetic control of gene transcription? |
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Definition
| Is independent of DNA sequence, effects are often heritable through cell division, is probably unique to eukaryotic cells, origin lies in differential packaging of chromosomal DNA, and dysfunction is increasingly recognized as an important pathological component |
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Term
| What part of histones are important for structure of individual nucleosomes? |
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Definition
| Helices. The amino terminal tails are important for packing nucleosomes together, but not for creating nucleosomes |
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Term
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Definition
| disk-shaped particle of 8 histone proteins encircled by approx 2 turns of DNA (~200 bp) |
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Term
| What is the role of histone tails? |
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Definition
| Help mediate internucleosomal contacts in the condensed 30 nm fiber via charge-charge interactions. I/a's include DNA-histone and histone-histone (to acidic amino acids in the globular region) |
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Term
| What is the component of histone tails? |
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Definition
| Positive (basic) amino acids |
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Term
| How does chromatin decondensation occur? |
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Definition
| Histone tails are neutralized by acetylation of lysines, which eliminate charge-charge interactions. |
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Term
| What are histone acetylases (HATs) |
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Definition
| They acetylate lysines of histones, leading do chromosome decondensation. They are generally co-activators of transcription, but are not DNA-binding factors but are still TF |
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Term
| What are histone deacetylases (HDACs) |
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Definition
| Deacetylate lysines in histone tail, leading to chromatin condensation. HDACs are typically co-repressors of transcription but are not DNA-binding factors. |
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Term
| Other than chromatin condensation, what is another function of acetylated lysine residues? |
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Definition
| They can represent recognition sites for other proteins that can then bind and further affect chromatin structure and transcriptional control |
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Term
| What are chromatin remodelers? |
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Definition
| ATP-dependent co-activators that move around or displace nucleosomes |
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Term
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Definition
| It is a TF that acts as a co-activator by disrupting local chromatin structure (has HAT activity) and helping to recruit the basal transcription machinery |
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Term
| What are the chromatin structure characteristics of active genes |
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Definition
| active (open) chromatin, unmethylated cytosines, acetylated histones |
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Term
| What are the chromatin characteristics of repressed genes |
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Definition
| Silent (condensed) chromosomes, methylated cytosines, deacetylated histones |
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Term
| What causes methylation of cytosine |
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Definition
| Methylation catalyzed by DNA methyltransferase (DNMT) at CpG in and around genes |
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Term
| What are amino acid modifications in chromatin? |
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Definition
| lysine acetylation, lysine and arginine methylation, serine phosphorylation, Cytosine methylation |
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Term
| Predominant means of gene regulation in prokaryotes |
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Definition
| Control of gene transcription |
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