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Summary Chapter 15 genetics
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- Genetics
- Instelling
- Vrije Universiteit Amsterdam (VU)
Chapter 15 genetics biomedical sciences vu
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CHAPTER 15Gene regulation is necessary to ensure:
1. Expression of genes in an accurate pattern during the various
developmental stages of the life cycle.
2. Differences among distinct cell types (nerve, muscle cells).
3. Homeostasis
4. Response to changes
15.1 REGULATORY TRANSCRIPTION FACTORS
Transcription factors are proteins that influence the ability of RNA
polymerase to transcribe a gene.
TYPES
- General transcription factors
Required for the binding of the RNA polymerase to the core promoter and its progression
to the elongation stage.
Necessary for basal transcription.
- Regulatory transcription factors
Regulate the rate of transcription of nearby genes.
They influence the ability of RNA pol to begun transcription of a particular gene.
RNA polymerase and its transcription factors: (review chapter 12)
Three categories of proteins are required for basal transcription to occur at the promoter.
- RNA polymerase II
- 5 protein complexes – GTFs
- Mediator
Regulatory transcription factors recognize cis regulatory elements located near the core
promoter. These sequences are known as response elements, control elements,
regulatory elements, cis-acting elements.
This binding affects the transcription of an associated gene.
- A regulatory protein that increases the rate of transcription is termed
an activator, The sequence it binds is called an ‘enhancer’
- A regulatory protein that decreases the rate of transcription is termed
a repressor, The sequence it binds is called an ‘silencer.
Eukaryotic genes are regulated by many factors, this is called combinatorial control because the
combination of many factors determines the expression of any given gene.
At the level of transcription, the following factors contribute to combinatorial control:
- One or more activator proteins may stimulate transcription
- One or more repressor proteins may inhibit transcription. Activators and repressors may be
modulated by:
• binding of small effector molecules
• protein-protein interactions
• covalent modifications
- Regulatory proteins may alter nucleosomes near the
promoter.
- DNA methylation may inhibit transcription by
• prevent binding of an activator protein
• recruiting proteins that compact the chromatin
- The formation of heterochromatin.
, STRUCTURAL FEATURES OF REGULATORY TRANSCRIPTION FACTORS
Transcription factor proteins contain regions, called domains, that have specific functions.
- DNA-binding
- Another domain could bind to other transcription factors
- Provide a binding site for 'effector' molecules / ligands
A ‘motif’ is a domain, or a portion of a domain, that has a very similar structure in many different
proteins.
REGULATORY TRANSCRIPTION FACTORS RECOGNIZE REGULATORY ELEMENTS THAT FUNCTION
AS ENHANCERS OR SILENCERS
- The binding of a transcription factor to an enhancer increases the rate of transcription.
This up-regulation can be 10- to 1,000-fold.
- The binding of a transcription factor to a silencer decreases the rate of transcription
This is called down-regulation.
Regulatory elements are orientation-independent or bidirectional. Such regulatory
sequence can function in the forward or reverse orientation.
Most response elements are located within a few hundred nucleotides upstream of the
promoter. Some are found at various other sites:
- Several thousand (even 100’000) nucleotides away
- Downstream from the promoter
- Even within introns (usually first intron)
GTFs: TFIID AND MEDIATOR
Regulatory transcription factors influence the ability of RNA polymerase to transcribe a gene.
Most RTfs do not bind directly to RNA polymerase.
Three common interactions that communicate the effects of regulatory transcription factors are:
1. Regulation via TFIID (multi-subunit general transcription
factor) either directly or through coactivators.
2. Regulation via Mediator.
3. Regulation via changes in chromatin structure.
REGULATION VIA TFIID
TFIID binds to the TATA box and recruits RNA pol to the core promoter.
Activator proteins can enhance the ability of TFIID to initiate transcription.
a) Transcriptional activation via TFIID.
The activator/coactivator complex recruits TFIID to the core promoter and activates its function.
Transcription will be activated.
b) Transcription repression via TFIID.
Repressors inhibit the function of TFIID. They could exert their effects by preventing the binding of
TFIID to the promoter.
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