Flashcards in Trans - Regulation of Gene Expression Deck (78)
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Importance of regulation of gene expression (3), give examples of each
1. adaptation to environmental changes --> ex. memory B cell antibody production during immune response
2. development --> ex. pluripotential stem cells
3. differentiation of cells --> ex. specific proteins for specific cell function
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Levels of eukaryotic gene regulation (6)
1. epigenetic control
2. transcriptional control
3. post-transcriptional control
4. RNA transport control
5. Translational control
6. Post-translational control
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Heterochromatin vs Euchromatin
1. heterochromatin --> dense, transcriptionally silent, tightly packed, inaccessible to polymerases and other enzymes
2. euchromatin --> loosely packed and active in gene transcription
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Define differential gene expression
Some genes are expressed while others are repressed
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a) structure and b) significance of telomeres
a) complexes of DNA and proteins at the end of chromosomes
b) maintain structural integrity, prevent attack by nucleases, allow repair systems to differentiate between ends and breaks
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Mechanisms to increase/decrease access to DNA sequence (2)
1. gene regulatory proteins
2. RNA polymerases
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Mechanisms to alter chromatin structure (2)
1. cytidine methylation
2. histone methylation
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Old and new concepts related to genetic switches
Old: "loss" of genesNew: genes can be turned "on" or "off"
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Principle of DNA methylation
[1] Silencing genes to reduce unnecessary gene expression
[2] Methylation of CG dinucleotide (CpG) in promoter causes silencing of genes
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Principle of DNA methylation
[1] Silencing genes to reduce unnecessary gene expression
[2] Methylation of CG dinucleotide (CpG) in promoter causes silencing of genes
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CpG
Cytosine-phosphate-guanine
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Characteristic of promoter region related to methylation
10-20x more CpG dinucleotides --> more affected by methylation
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Effect of methylation on promoter
[1] High methylation / hypermethylation --> transcriptionally silent
[2] Low methylation / hypomethylation --> transcriptionally active
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Other effects of methylation
Prevent binding of regulatory factors by stearic hindrance
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Mediators of methylation
MeCP1 and MeCP2 (Methylated CpG binding proteins 1 & 2)
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Fragile X syndrome
Mental retardation caused by expansion of CGG at 5' UTR of FMR1 gene --> increased methylation causing silencing of FMR and brain-specific mRNA during development
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Histones
Order DNA into nucleosomes, (+) charged due to high lysine and arginine content --> form ionic bonds with (-) charged DNA
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Principle of histone acetylation
Acetyl groups attached to lysine in histone, forming tails that protrude from the nucleosome --> repulsion between tails causes more open DNA structure
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Effect of histone acetylation
More acetylation --> more open DNA structure --> more accessible for transcription
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Histone aminotransferases - function?
Eliminate positive charge on lysine, decreasing interaction of histone and negative DNA
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Histone deacetylases - function?
Restore positive charge of lysine, increasing interaction of histone and negative DNA
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Relationship between DNA methylation and histone acetylation
Reciprocal --> when DNA is methylated, histone is deacetylated, and vice versa
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Sites of histone methylation to hinder transcription
Histone H3 lysine 9, 27
Histone H4 lysine 2
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Sites of histone methylation to enhance transcription
Histone H3 lysine 4, 27, 36
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Effect of histone methylation
Activate or deactivate DNA, depending on methylation site
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Ubiquitin - function?
Marks defective protein for destruction
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Effects of histone ubiquitination
[1] disruption and spreading of chromatin allowing binding of transcription proteins;
[2] binding of effector proteins for other regulatory processes;
[3] allows other histone modifications to occur
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Principle of histone ubiquitination
Attachment of ubiquitin to histone in order to modulate gene expression
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Histone ubiquitination is required for these specific regulatory processes
di- and tri- methylation of H3 lysine 4 and lysine 79
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