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L2 - TRANSCRIPTIONAL REGULATION Be able to draw the basic structure of a…
L2 - TRANSCRIPTIONAL REGULATION
- Be able to draw the basic structure of a gene including;
promoter, TATA box, transcriptional start site, 5’untranslated region, start codon, exons, introns, coding sequence, stop
codon, 3’untranslated region.
- Be able to describe the three steps in the Central Dogma.
- Understand that gene expression is regulated at many levels and may be cell-type specific
- Be able to describe the terms transcription factor, master regulator, auto-regulatory loop and hierarchical transcription factor cascade.
- Be able to give an example of transcription factor availability (localization/concentration) as a mechanism for regulating gene expression
- Define the role of local chromatin conformation in transcriptional regulation, including nucleosome occupancy and enhancer-promoter interactions.
- Define the role of large-scale chromatin conformation on transcriptional regulation, including the role of nuclear organization
and TADs.
GENE STRUCTURE
Long term storgae of biological information - with near perfect fidelity/honesty - so mutations and evolution are seldom yet they can occur
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Central Dogma
DNA => RNA => Protein
Historically this is true, yet there new research demonstrates that some RNA is functional in and of itself - not all RNA translates into protein
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Gene Expression
Cellular identity is achieved through differential expression of the same genetic material(Nuclear repetoir). Despite having the same genome to draw from, cells achieve differentiation
Housekeeping Genes
Those genes whose expression is preserved throughout the diffeent cell typesE.g. Beta-actin (Cytoskeleton0
Alternative Genetic Expression is Regulated at many levels
External Stimuli Influence Genetic Expression
- Cell to cell contact
- Hormone
Morphogens - molecules that, in high concentration, specify cellular identity
Transcriptional Control
- Transcripton factors are Proteins which bind to regulatory elements of a gene
- These are often synthesised or activated in response to
external stimuli (eg hormone binding)
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By binding to a promoter/enhancer sequence they can silence or promote gene expression at that gene
The promoter integrates all the internal and external signals to determine the probability that the gene will be transcribed.
During development, TFs can act in hierarchical cascades to direct appropriate lineage restriction
Master Regulators
Transcription Factors at the top of the cascade, which activate other TFs lower down on thehierarchy, which each act on multiple genes/activate other TFs
C requires synergetic action by both A and B
A activates all the TF's of the lower hierarchy
Sequential activation
Master regulators can also be auto-regulatory – they
promoter their own transcription which reinforces
and strengthens the commitment to the specific
lineage they regulate
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Transcription, a means of regulation, is itself HIGHLY regulated
- Availability/concentration/localisation of transcription factors
- Competition between positive and negative regulatorv factors
- Local chromatin conformation (and epigenetics)
- Large-scale chromatin conformation
- The nuclear architecture
TF Localisation
Localising TF's in high concentrations increases their effect
e.g. When an external stimuli, ionomycin, acts on its target cell, rapid translocation of TF NFAT ensues. NFAT is a calcium responsive TF whch increases the cncentratio of Ca in the cell
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Assymetric distribution of TF's during cell division distinguishroles of daughter cells
Combinatorial Control
The combinations of Transcription Factors binding to DNA at sites in the PROMOTER and ENHANCER regions
Combinatorial control Influenced by;
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