Control of gene expression 1 Flashcards

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1
Q

Give details on controlling gene expression

A
  • gene expression is carefully controlled (highly regulated)
  • only genes needed for function of the cell will be expressed
  • some proteins are needed in large amounts whereas other in small
  • the levels of various proteins may need to go up and down in a given cell depending on the stage e.g. during the cell cycle
  • synthesis of unnecessary proteins is wasteful of cells energy and resources
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2
Q

What are 3 times when gene expression is regulated?

A
  1. During differentiation and development
  2. As a response to the environment
  3. Depending on the function of the cell
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3
Q

4 problems with regulation of gene expression?

A
  • cancer (absence of transcription off switch leads to wrong genes being expressed and cell division)
  • developmental disease (mistakes in early protein synthesis can lead to organ developmental problems)
  • exposure to toxins or drugs
  • chronic diseases (abnormal gene expression as a result of the wrong signals in the cell can cause inflammation)
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4
Q

What six levels is eukaryote gene expression regulated at?

A
  1. Transcription
  2. RNA processing
  3. mRNA transport
  4. mRNA translation
  5. mRNA degradation
  6. Protein degradation
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5
Q

Explain how transcription initiation can regulate gene expression

A

Transcription initiation is the major point of regulation in eukaryotic gene expression and is controlled by interactions between DNA and proteins.
This comes about by an interactions between DNA and proteins.
Proteins come and bind to the DNA.
Trans-acting molecules are ones which come from other areas not from the DNA. They are proteins.

This makes a transcription factor which goes back into the nucleus and binds to another place on the DNA sequence. This allows polymerase II to start transcribing this region.

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6
Q

Give 4 points on regulatory molecules

A
  • Proteins which control transcription initiation by binding to DNA
  • Can diffuse through the cell from its site of synthesis to bind to the regulatory sequence (such a promoter) and affect transcription
  • Usually have 2 domains, a DNA binding domain and a transcription activation domain
  • e.g. general transcription factors which are needed for transcription initation
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7
Q

Give 4 points on regulatory sequences

A
  • Short sequences of DNA which control transcription initiation
  • Usually found in the non-coding regions of the genome
  • Interact with DNA binding proteins e.g. transcription factors resulting in induction or repression of transcription initiation
  • Called ‘cis’ because they influence genes on the same DNA molecule
  • e.g. TATA box
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8
Q

What is TATA box?

A

a highly conserved promoter in eukaryotic DNA

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9
Q

Promoters:
Short sequence found —- of a coding region.
Important in the —- of transcription.
The site where the ‘—- —- —-‘ is assembled.

The TATA box helps to —- the RNA polymerase II for correct transcription initiation. There can be other regulatory sequences.

A

Upstream

Initiation

Transcription initiation complex

Position

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10
Q

What are transcription factors and what are the two types?

A

They are proteins which ensure that genes are correctly expressed at a specific time and in response to internal or external stimuli.

  1. General Transcription Factors: proteins which can bind DNA and are needed to form a pre-initiation complex and to recruit RNA Polymerase II
  2. Sequence-specific DNA binding TF: these facilitate or prevent transcription initiation of specific promoters
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11
Q

What are general transcription factors needed for?

A

Needed for all RNApol II transcribed genes.
The ‘core’ promoter is the one where RNA pol II and GTFs will bind.
The ‘proximal’ promoter is where other transcription factors will bind.

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12
Q

Give 3 steps in transcription initation

A
  • A transcription initiation complex has to assemble upstream of the start site which helps RNA polymerase II to get started. A specific order is needed of these transcription factors (8 of them in total).
  • A number of proteins have come together in a specific order to help RNA pol II transcribe genes. These are general transcription factors
  • The GTFs position RNA pol II at the promoter resulting in a transcription initiation complex. The polymerase then copies the DNA into RNA.
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13
Q

Regulation is achieved by the specific combination of protein factors in the —- —-

A

Initiation complex

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14
Q

What can a mutation in the coding sequence of a TF do?

A

Abnormal mRNA is produced, abnormal expression of proteins and an altered regulation of pathways.

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15
Q

Explain of regulation of gene expression by hormones:

A

Sometimes the signal to switch genes on/transcribe comes from a distant source in the body e.g. via the endocrine system
Hormones are exogenous chemicals released into circulation which can travel and affect target tissues
Hormones signals to switch genes on and off by binding to receptors in the cell membrane and starting a signalling cascade
The effect of hormones can stimulate synthesis of large amounts of protein in certain tissues (target tissues)
Some hormones enter the cell and then bind to a receptor, the receptor-hormone complex moves to the nucleus where is interacts with DNA and stimulates transcription of target genes (transcription initiation) to bring about a physiological change in the cell. Other hormones initiate a signalling cascade which can affect gene expression
The endocrine system can regulate and co-ordinate changes in gene expression of many systems.

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16
Q

What are the 5 steps in RNA expression?

A
  • Transcription initiation
  • RNA synthesis
  • 5’ capping
  • 3’ poly-adenylation
  • Splicing
17
Q

Give the details on the two types of regulation of mRNA processing

A

Polyadenylation

  • rare
  • U1A protein can bind its own mRNA just upstream of the polyA site. This inhibits the polyadenylation therefore the mRNA processing does not complete
  • When there is plenty of U1A protein, the mRNA is inhibited, when U1A protein levels drop, the mRNA can be polyadenylated and more U1A protein can be made.

Splicing

  • more common in humans
  • differntial splicing can give rise to very different proteins
  • e.g. fibronectin is different in liver and fibroblasts so it can have different functions
18
Q

An example using U1A protein:
When U1A is high, what does it do?
When low?

A

Binds the pre-mRNA and inhibits poly-adenylation.

Not enough of it to bind the pre-mRNA, which can then get poly-adenylated and the mature U1A mRNA can then be used to make more U1A protein by translation.

19
Q

Explain what alternative splicing is

A
  • highly regulated process during gene expression
  • all introns are removed by splicing - this is part of normal RNA processing
  • some exons are selectively removed alternative splicing - This way a single gene can give rise to multiple proteins by alternative splicing.