Topic 8 - Gene Expression Flashcards
What is potency?
The ability to differentiate into specialised cells
What is self-renewal?
The ability to replicate indefinitely
What is the cell type with the highest potency?
Totipotent Stem Cells
What is the cell type with the lowest potency?
Unipotent Stem Cells
What is a totipotent stem cell?
- Able to produce any type of body cell as well as cells of supportive structures such as the placenta.
- They are the most unspecialised stem cell.
- Totipotent cells can translate only part of their DNA, resulting in cell specialisation.
- Totipotent cells occur only for a limited time in early embryos.
What is a pluripotent stem cell?
- Embryonic stem cells that can differentiate into any cell type found in an embryo.
- Pluripotent stem cells can divide in unlimited numbers and can be used in treating human disorders.
What is a multipotent stem cell?
- Found in mature mammals and can differentiate into a limited number of cell types.
- For example, multipotent cells in the bone marrow can produce a range of blood cells.
What is a unipotent stem cell?
- The most differentiated cells, they can produce only one cell type but have the property of self-renewal that distinguishes them from non-stem cells.
- Unipotent cells can form new heart cells (cardiomyocytes) which can be generated from unipotent cardiac progenitor cells (CPCs).
What is an induced pluripotent stem cell (iPSC)?
- Induced pluripotent stem cells are adult specialised cells that have been ‘reprogrammed’ so that they behave like embryonic stem cells.
- iPS cells can be produced from adult somatic cells using transcription factors which dedifferentiate a cell back to its pluripotent state.
What is a promotor region?
Sequence of DNA, with a specific code which transcription factors bind to.
What is a transcription factor?
A protein that controls the transcription of genes by binding to a specific region of DNA (from DNA to mRNA)
Describe the process of a transcription factor controlling transcription
1) The transcription factor (Tf) binds to the complementary promotor region of the mRNA strand, ‘upstream’ from the gene.
2) RNA polymerase binds to the Tf, activating it.
3) RNA polymerase binds before the gene, causing the mRNA strand to ‘bend’.
4) Transcription is then activated by the RNA polymerase binding to the mRNA strand.
What is interference RNA (siRNA)?
- The use of small interfering RNA to prevent translation of a gene.
- siRNA has a short sequence of around 25 nucleotides.
Describe the process of siRNA in preventing the translation of a gene.
1) mRNA is transcribed as normal.
2) RDR polymerase (RNA-dependent RNA) in the cytoplasm turns the mRNA into dsRNA.
3) An enzyme called DICER then breaks down the dsRNA.
4) siRNA then bonds to a protein complex called RISC.
5) RISC breaks down the dsRNA to result in a RISC protein with a single RNA strand attached.
6) The risk then binds to and breaks down complementary mRNA, preventing it from being translated.
What is oestrogen?
- Steroid hormone
- Lipid soluble
- Hydrophobic
- Can enter cells via diffusion
How does oestrogen control the transcription of genes?
Oestrogen enters a cell and binds to a protein called ERα (Osetrogen Receptor Alpha) and forms a complex, which results in being a transcription factor.
What is epigenetics?
Epigenetics involves heritable changes in gene function, without changes to the base sequence of DNA.
What is epigenetics caused by?
Caused by an environmental trigger (no mutation)
How to changes in the environment lead to inhibition of transcription?
The changes are caused by changes in the environment that inhibit transcription by:
1) Increased methylation of the DNA
2) Decreased acetylation of associated histones.
What is methylation?
- Methyl group (CH3) is added to the carbon atom of cytosine bonds in DNA.
- This suppresses transcription and switches the gene off by altering/changing the shape of the DNA
What is acetylation?
- COCH3 is added to lysine group of the histone, removing H+.
- DNA becomes less attracted and unwinds slightly.
- This increases transcription
What is deactylation?
- COCH3 group removed, adding H+
- DNA becomes more attracted
- Decreases transcription
What are benign tumours?
- Not cancerous
- They usually grow slower than malignant tumours.
- Often covered in fibrous tissues that stop cells from invading other tissues.
- Often harmless, but can cause blockages or put pressure on organs.
- Some can become malignant.
What are malignant tumours?
- Cancers
- They usually grow rapidly and invade and destroy surrounding tissues.
- Cells can break off the tumours and spread to other parts of the body in the bloodstream or lymphatic system.
What are tumour cells?
- Have an irregular shape
- Have a longer and darker nucleus than normal cells
- Don’t respond to growth regulating processes.
- Have different antigens on their surface
- Divide by mitosis more frequently than normal cells
What are tumour suppressor genes?
- Tumour suppressor genes can be inactivated if a mutation occurs in the DNA sequence.
- When functioning normally, tumour suppressor genes slow cell division by producing proteins that stop cells from dividing or cause them to self-destruct (apoptosis)
- If a mutation occurs in a tumour suppressor gene, the protein isn’t produced. The cells divide uncontrollably, resulting in a tumour.
What are oncogenes?
- The effect of a proto-onco gene can be increased if a mutation occurs in the DNA sequence.
- A mutated proto-onco gene is called an onco-gene.
- When functionally normally, proto-onco genes stimulate cell division by producing proteins that make cells divide.
- If a mutation occurs in a proto-onco gene, the gene can become overactive. This stimulates the cells to divide uncontrollably, resulting in a tumour.
How does the abnormal methylation of tumour suppressor genes lead to the formation of tumours?
When tumour suppressor genes are hypermethylated, the genes are not transcribed, so the proteins they produce to slow cell division aren’t made. This means that cells are able to divide uncontrollably by mitosis, and tumours can develop
How does the abnormal methylation of oncogenes lead to the formation of tumours?
Hypomethylation of proto-oncogenes causes them to act as oncogenes, increasing the production of the proteins that encourage cell division. This stimulates cells to divide uncontrollably, which causes the formation of tumours.
Why do increased oestrogen concentrations lead to the development of some breast cancers?
Increased exposure to oestrogen over an extended period of time is thought to increase a woman’s risk of developing breast cancer.
What are the 3 theories about how oestrogen can contribute to the development of some breast cancers?
1) Oestrogen can stimulate certain breast cells to divide and replicate. The fact that more mitosis is occurring, increases the risk of mutation and of cells becoming cancerous.
2) This ability to stimulate division could also mean that if cells do become cancerous, their rapid replication could be further assisted by oestrogen, helping tumours to form quickly.
3) Other research suggests that oestrogen is able to introduce mutations directly into the DNA of certain breast cells, again increasing the chance of these cells becoming cancerous.