Read the summary and the most important questions on Week 1 Day 1: Gene Expression

• 1 Gene expression: the basics

• 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 thyroid hormones and other molecules. In response, these receptors work with other proteins 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 bp motifs through a much larger number of individually weak intermolecular 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.