BBOL-Regulation of gene expression Flashcards

1
Q

What is spatial control?

A

Involves location of cell and the environment that surrounds it

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2
Q

What is temporal control?

A

When genes require expression, e.g. staged of foetal developmental

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3
Q

How is protein production controlled?

A
  • Control can be exerted at every step from DNA to protein
  • Genes can be regulating transcription itself or by post-transcriptional regulation
  • Transcriptional control, RNA processing control, RNA transport and localisation control, mRNA degradation control and protein activity control
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4
Q

Describe transcriptional control

A
  • Regulation of transcription is the most common form of control for protein production
  • Binding of RNA polymerase: promoters and transcription factors
  • Long range control- locus control regions
  • Chromatin remodelling- histones and histone deacetylases
  • DNA methylation- CpG islands and imprinting
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5
Q

What proteins control gene expression?

A
  • Transcription factos bind to DNA in the major groove of the double helix
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6
Q

What are DNA binding motifs?

A
  • Gene regulatory proteins contain these and they are part of the protein that binds to DNA
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7
Q

How do gene switches work?

negative regulation

A
  • Bound repressor protein prevents transcription
  • Ligand binds to remove reg. protein from DNA
  • Addition of ligand switches gene on by removing repressor protein
  • Ligand binds to allow regulatory protein to bind to DNA
  • Removal of ligand switches gene on by removing repressor protein
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8
Q

How do gene switches work?

positive regulation

A
  • Bound activator protein promotes transcription
  • Ligand binds to remove regulatory protein from DNA
  • Addition of ligand switches gene off by removing activator
  • Removal of ligand switches gene off by removing activator protein
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9
Q

What do repressors do?

A
  • Turn genes off
  • Prokaryotes co-ordinately regulate related genes by clustering them: operon
  • Genes can be regulated by environmental signals, e.g. tryptophan repressor
  • Tryptophan repressor binds to the operon promoter and turns transcription off
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10
Q

What do activators do?

A
  • Bind to promoter and interact with RNA polymerase to initiate transcription
  • In bacteria, binding of activator to DNA controlled by interaction of a metabolite or other small molecule
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11
Q

How are prokaryotic genes controlled by multiple signals?

A
  • Lac operon controlled by 2 signals- activator and repressor
  • Controls synthesis of B-galactosidase that breaks down lactose to glucose in growth medium control activity of repressor and activator
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12
Q

How are eukaryotic genes controlled?

A
  • General transcription factos needed for all genes
  • Gene specific regulation provided by different combinations of regulatory proteins
  • Regulatory binding sites may be upstream (5’) , in introns or downstream (3’) of gene (DNA looping facilitates interaction)
  • Multiple regulatory transcription factors regulate any one gene
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13
Q

How does regulation occur over long distances?

A
  • Some control elements are many 100s of base pairs from the gene
  • Can control activation of several nearby genes through chromatin remodelling- Locus Control Region (LCR)
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14
Q

How is transcription factor (TF) activation regulated?

A
  • Activity of regulatory TF may be controlled by protein synthesis, covalent mod, ligand or inhibitor binding that sequester the protein or affect DNA binding ability
  • E.g. hormone receptor binding in response to ligand binding
  • Ligand binding to GPCRs can lead to gene activation through intracellular signalling pathway- TF activation
  • Binding of inflammatory cytokine TNFa leads to degradation of inhibitor protein and activation of NFkB
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15
Q

Describe epigenetics

A
  • Changes made to DNA that do not involve changes to the sequence
  • Control of ‘packaging’
  • Chromatin regulation (for DNA to loop and allow regulatory protein interaction accessible and chromatin can remodel in response to activator binding and acetylation pattern of histones can allow recognition and binding by activators)
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16
Q

What are HDAC inhibitors in cancer?

A
  • Opposing actions of histone acetyltransferase and histone deacetylase regulate gene expression through chromatin remodelling
  • Aberrant transcription due to altered gene expression or mutation of genes that encode HATs, HDACs or their binding partners is a key progression of cancer
  • HDAC inhibitors can reactivate gene expression and inhibit growth/survival of tumour cells
17
Q

Describe X inactivation

A
  • Females have 2 copies of each X chromosome
  • Early development, 1 inactivated (dosage compensation)
  • Inactive X becomes highly condensed
  • Mediated by the XIST gene transcript
18
Q

Describe DNA methylation

A
  • DNA can become methylated at specific cytosine residues (CpG sites)
  • Methylated can turn gene expression
  • Methylated patterns can be inherited (maternal and paternal imprinting)
19
Q

What is post transcriptional regulation?

A
  • Can occur at every step between transcription and translation
  • mRNA processing: alternative splicing and RNA editing
  • mRNA export: nuclear export is controlled, quality control of transcription and splicing
  • mRNA localisation: mRNA can be directed to specific areas in cytoplasm for local protein production
  • Negative translational control: 5’ and 3’ UTR binding proteins and miRNAs can regulate translation
  • Regulation of mRNA stability: allows more immediate response to environment than control of transcription
20
Q

Describe post-translational control

A
  • Protein degradation is also under active control

- Proteins are targeted for degradation by the proteasome by ubiquitin conjugation

21
Q

How is protein production controlled?

A
  • Epigenetic processes and promoters involved in transcriptional control
  • Post-translational modification and protein degradation involved in protein activity control