gene expression Flashcards
What are stem cells?
*Undifferentiated / unspecialised cells capable of:
1. Dividing (by mitosis) to replace themselves indefinitely
2. Differentiating into other types of (specialised) cells
Describe how stem cells become specialised during development
*Stimuli lead to activation of some genes (due to transcription factors - see 8.2.2)
● So mRNA is transcribed only from these genes and then translated to form proteins
● These proteins modify cells permanently and determine cell structure / function
Describe totipotent cells
● Occur for a limited time in early mammalian embryos
● Can divide AND differentiate into any type of body cell (including extra-embryonic cells eg. placenta)
Describe pluripotent cells
● Found in mammalian embryos (after first few cell divisions)
● Can divide AND differentiate into most cell types (every cell type in the body but not placental cells)
Describe multipotent cells
● Found in mature mammals
● Can divide AND differentiate into a
limited number of cell types
Describe unipotent cells, using an example
● Found in mature mammals
● Can divide AND differentiate into just one cell type
Example: unipotent cells in the heart can divide and differentiate
into cardiomyocytes (cardiac muscle cells)
Explain how stem cells can be used in the treatment of human disorders
● Transplanted into patients to divide in unlimited numbers
● Then differentiate into required healthy cells (to replace faulty / damaged cells)
Explain how induced pluripotent stem (iPS) cells are produced
- Obtain adult somatic (body) cells (non-pluripotent cells or fibroblasts) from patient
- Add specific protein transcription factors associated with pluripotency to cells so express genes associated with pluripotency (reprogramming)
○ Transcription factors attach to promoter regions of DNA, stimulating or inhibiting transcription - Culture cells to allow them to divide by mitosis
Evaluate the use of stem cells in treating human disorders
For:
* can divide and differentiate into required healthy cells, so could relieve human suffering by saving lives and improving quality of life
- embryos are often left over from IVF and so would otherwise be destroyed.
- iPS cells unlikely to be rejected by patient’s immune system as made with patient’s own cells.
*iPS cells can be made without destruction of embryo and adult can give permission
Against:
*ethical issues with embryonic stem cells as obtaining them requires destruction of an embryo and potential life (embryo cannot consent)
*Immune system could reject cells and immunosuppressant drugs are required
*cells could divide out of control, leading to formation of tumours / cancer
Examples of treatments using stem cells
● Potential treatment of Type 1 diabetes by creating healthy islet cells that produce insulin
● Bone marrow stem cell transplant for sickle cell disease / blood cancers
1. Destroy patient’s bone marrow before treatment → so no faulty cells are produced
2. Transplant stem cells from healthy person → divide and differentiate into healthy cells
What are transcription factors?
● Proteins which regulate (stimulate or inhibit) transcription of specific target genes in eukaryotes
● By binding to a specific DNA base sequence on a promoter region
Describe how transcription can be regulated using transcription factors
- Transcription factors move from cytoplasm to nucleus
- Bind to DNA at a specific DNA base sequence on a promoter region (before / upstream of target gene)
- This stimulates or inhibits transcription (production of mRNA) of target gene(s) by helping or preventing RNA polymerase binding
Explain how oestrogen affects transcription
- Oestrogen is a lipid-soluble steroid hormone so diffuses into cell across the phospholipid bilayer.
- In cytoplasm, oestrogen binds to its receptor, an inactive transcription factor, forming an oestrogen-receptor complex
- This changes the shape of the inactive transcription factor, forming an active transcription factor
- The complex diffuses from cytoplasm into the nucleus
- Then binds to a specific DNA base sequence on the promoter region of a target gene
- Stimulating transcription of target genes forming mRNA by helping RNA polymerase to bind
Explain why oestrogen only affects target cells
Other cells do not have oestrogen receptors
What is RNA interference (RNAi)?
● Inhibition of translation of mRNA produced from target genes, by RNA molecules eg. siRNA, miRNA
● This inhibits expression of (silencing) a target gene
Describe the regulation of translation by RNA interference
*siRNA/miRNA binds to a protein,
*forms an RNA-induced silencing complex (RISC)
*single stranded miRNA / siRNA within RISC binds to target mRNA with a comp base sequence.
*leads to hydrolysis of mRNA into fragments which then degraded OR prevents ribosomes binding.
*reducing / preventing translation of target mRNA into protein
Describe what is meant by epigenetics
● Heritable changes in gene function / expression without changes to the base sequence of DNA
● Caused by changes in the environment (eg. diet, stress, toxins)
Describe what is meant by epigenome
All chemical modification of DNA and histone proteins - methyl groups on DNA and acetyl groups on histones
To inhibit transcription
methylation increased and acetylation decreased
Allow transcription
methylation decreased and acetylation increased
Explain how methylation can inhibit transcription
- Increased methylation of DNA - methyl
groups added to cytosine bases in DNA - So nucleosomes (DNA wrapped around
histone) pack more tightly together - Preventing transcription factors and
RNA polymerase binding to promoter
Explain how low acetylation can inhibit transcription
- Decreased acetylation of histones
increases positive charge of histones - So histones bind DNA (negatively
charged) more tightly - Preventing transcription factors and
RNA polymerase binding to promoter
Describe how tumours and cancers form
● Mutations in DNA / genes controlling mitosis can lead to
uncontrolled cell division
● Tumour formed if this results in mass of abnormal cells
○ Malignant tumour = cancerous, can spread by metastasis
○ Benign tumour = non-cancerous
Describe the function of tumour suppressor genes
Code for proteins that:
● Inhibit / slow cell cycle (eg. if DNA damage detected)
● OR cause self-destruction (apoptosis) of potential tumour cells (eg. if damaged DNA can’t be repaired)
Explain the role of tumour suppressor genes in the development of tumours
● Mutation in DNA base sequence → production of non-functional protein
○ By leading to change in amino acid sequence which changes protein tertiary structure
● Decreased histone acetylation OR increased DNA methylation → prevents production of protein
○ By preventing binding of RNA polymerase to promoter region, inhibiting transcription
● Both lead to uncontrolled cell division (cell division cannot be slowed)
Describe the function of (proto-)oncogenes
Code for proteins that stimulate cell division
(eg. through involvement in signalling pathways that control cell responses to growth factors)
Explain the role of oncogenes in the development of tumours
● Mutation in DNA base sequence → overproduction of protein OR permanently activated protein
○ By leading to change in amino acid sequence which changes protein tertiary structure
● Decreased DNA methylation OR increased histone acetylation → increases production of protein
○ By stimulating binding of RNA polymerase to promoter region, stimulating transcription
● Both lead to uncontrolled cell division (cell division is permanently stimulated)
What is an oncogene
An oncogene is a mutated / abnormally expressed form of the corresponding proto-oncogene
Suggest why tumours require mutations in both alleles of a tumour suppressor gene but only one allele of an oncogene
● One functional allele of a tumour suppressor gene can produce enough protein to slow the cell cycle
OR cause self-destruction of potential tumour cells → cell division is controlled
● One mutated oncogene allele can produce enough protein to lead to rapid / uncontrolled cell division
Explain the role of increased oestrogen concentrations in the development
of some (oestrogen receptor-positive) breast cancers
*some breast cancers cells have oestrogen receptors,
*If oestrogen concentration is increased, more oestrogen binds to oestrogen receptors, form more oestrogen-receptor complexes which are active transcription factors.
3. These bind to promoter regions of genes that code for proteins stimulating cell division.
4. This increases transcription / expression of these genes, increasing the rate of cell division
Suggest how drugs that have a similar structure to oestrogen help treat
oestrogen receptor-positive breast cancers
● Drugs bind to oestrogen receptors (inactive transcription factors), preventing binding of oestrogen
● So no / fewer transcription factors bind to promoter regions of genes that stimulate the cell cycle.
Differences between malignant and benign tumours
*malignant- spread by metastasis - cells break off and spread to other parts of the body benign doesnt metastasise
*mal- grow faster, ben slower
*mal- cells have irregular nuclei, ben- normal, regular nuclei
*mal- poorly differentiated/specialised, ben- well diffrentiated/specialised
Where is oestrogen produced in women with menopause
the fat cells in the breast tissue
Explain the relevance of epigenetics in cancer treatment
● Increasing DNA methylation OR decreasing histone acetylation of oncogene
○ To inhibit transcription / expression
● Decreasing DNA methylation OR increasing histone acetylation of tumour suppressor gene
○ To stimulate transcription / expression
