Summary: Week 1 Day 1: Gene Expression
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1 Gene expression: the basics
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1.1 Transcription factors
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What is a transcription factor (TF)?
Any biochemical factor involved in transcription –including water, salt, DNA, NTPs and the protein factors such as RNA polymerase II, other general/basal factors plus protein co-factors such as those involved in chromatin, elongation etc. -
Co-factors (co-regulators/co-activators/co-repressors)
Required to achieve appropriate regulation but not in themselves required for specificity (chromatin, remodelers, modifiers) -
P.I.C. (PreInitiation Complex)
Consists of at least RNApol II and general transcription factors (TFIIA, TFIIB, TFIID, TFIIE, TFIIF, and TFIIH). -
Nuclear Receptor (NR)
A class of proteins found within cells that are responsible for sensing steroid and thyroidhormones and other molecules. In response, thesereceptors work with otherproteins to regulate the expression of specific genes. -
1.3 General build-up of GTTFs
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DNA binding domain (DBD)
Binds in particular to major groove, recognizing 4-8 bpmotifs through a much larger number of individually weakintermolecular interactions . -
Activation domain (AD)
Protein-protein interaction domain; classified by the tendency of certain amino acids, e.g. glutamine-rich or proline-rich. -
1.5 How do GSTFs bind spesific sequences?
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How do GSTFs bind specific sequences?
Bind mostly at major groove: more space but more importantly, presents more specific chemical groups that allows better distinction between different base-pairs. -
Binding motifs: Position Weight Matrices (PWM)
Representation of the “frequency distribution” of bases at different positions in the motif. -
1.7 The ligand-dependent activation domain
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Ligand Binding Domains (LBDs)
Variable in sequence but similar in fold. -
Squelcing/Transcriptional interference
Liganded NRs can inhibit each other's activity.
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