Lec20 - Lecture 20 Eukaryotic Gene Regulation 2 REGULATORY...

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Lecture 20 Eukaryotic Gene Regulation 2 REGULATORY TRANSCRIPTION FACTORS & ACTIVATION MECHANISMS Lodish 6th edition Chapter 7 Lodish 5th edition Chapter 11
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Promoter Enhancer (or Silencer) Core Promoter Elements Proximal Regulatory Elements Enhancer (or Silencer) Distal Regulatory Elements General (Basal) Transcription Machinery RNA polymerase II (Pol II) + General/Basal Transcription Factors (TFII A, B, D, E, F, H) (analogy to prokaryotic Polymerase core + Sigma Factors) Present in all cells & used by all protein-coding genes. Transcription start site recognition. Regulatory Transcription Factors Gene-specific or cell-specific DNA-binding activators and repressors (analogy to CAP and NtrC activators in bacteria) Regulate binding/recruitment of general transcription factors to core promoter. Influence transcription initiation and elongation DNA Promoter Structure and Transcription Factors for Eukaryotic Class II (protein-coding) Genes Enhancer: DNA sequences usually containing several transcription factor binding sites that can activate transcription over long distances independently of their position and orientation relative to a gene: i.e. when placed far (several kb) upstream or downstream of a gene and in either polarity --> or <-- (Silencers have similar properties but instead repress transcription). Gene
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Regulatory transcription factors are modular Acidic (E/D-rich) Proline-rich Glutamine-rich others Flexible hinge DNA (highly structured; recognition of specific DNA sequences) Activation domain DNA-binding domain (communication with general transcription factors/Pol II; usually poorly structured ) core promoter GTFs & Pol II CACGTG Activator-specific DNA recognition sequence “stimulation” GTFs & Pol II Recruitment (direct or indirect) Post-recruitment steps (DNA unwinding, initiation, promoter clearance and elongation) Sequence-specific activator
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Different DNA-binding motifs specify distinct families of regulatory transcription factors 1. Helix-turn-helix (HTH) DNA-binding motif found in a variety of globular transcription factors including Homeodomain proteins (i.e. products of homeotic genes) that specify parts/segments of the body and in other HTH variant proteins (winged-helix proteins, Pou domain proteins, and Paired domain proteins). Homeodomain of Engrailed protein interacting with its specific DNA site: (Fig. 10-40 in Lodish 4th Ed.) Recognition helix
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2. Basic region/Helix-Loop-Helix/leucine Zipper (bHLHZip) DNA-binding and dimerization motifs found in different combinations in a variety of coiled-coil/fibrous transcription factors that include: basic/leucine zipper ( bZip ) Basic/Helix-Loop-Helix ( bHLH ), and basic-Helix-loop-Helix-Zipper ( bHLHZip ) proteins.
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Lec20 - Lecture 20 Eukaryotic Gene Regulation 2 REGULATORY...

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