Enhancers and Silencers

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Enhancers and Silencers
Elements that are not a part of the promoter but
can either enhance (enhancer) or inhibit
(silencer) transcription at a manner that is
position- and orientation-independent.
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How do enhancers work?

• An enhancers binds transcription factors
  (activators) to activate transcription
• An enhancer can be located upstream, within, or
  downstream of a gene.

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Transcription Activators have Modular Structures
DNA-binding Domains Zinc Fingers (TFIIIA, Sp1)
Homeo Domains (Homeobox proteins) bZip and
bHLH motifs (C/EBP, MyoD)
Activation Domains Acidic Domains (Gal4, VP16)
Glutamine-rich Domains (Sp1) Proline-rich
Domains (CTF)
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Experiments with Chimera
Transcription activators have modular structure
- DNA-binding domain and activating domain
- They can function independently
Activators
Enhancers
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GAL4 Stimulates Pre-initiation Complex Formation
Crude extract
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Acidic Activation Domain of VP16 interacts with
TFIID
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Binding of TFIIB is a Rate-Limiting Step in the
Formation of Pre-initiation Complex
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The TBP-Associated Proteins (TAFs)
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(No Transcript)
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(No Transcript)
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A Model for Activation by CREB
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Transcription Activation
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A Model for Activation by Steroid Hormone
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One Factor can Relay Multiple Responses
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Signal Transduction Activates Transcription
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A Typical Promoter has Multiple Binding Sites for
Regulatory Proteins
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Significance of Multiple Factors
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Physiological Significance of Dimerization
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Leucine-zipper dimer
GCN4
Leucine-zipper Heterodimer Confers Different
Specificity
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Helix-loop-helix Homo- and Hetero-dimers
Inhibitor
MyoD
MyoD-Id