8 The Control of Gene Expression- Gene Expression Flashcards
What are stem cells and what are they capable of?
Unspecialised cells; capable of dividing & differentiating into any type of cell
Types of stem cells; what are totipotent cells and their function?
-Exist only for a very limited time during embryonic development in mammals (first few cell divisions)
-During development, totipotent cells translate only part of their DNA—> cells remain unspecialised
-Are able to produce any type of body cell, cells of supportive structures like the placenta
-Are the most unspecialised stem cell, specialise into many different cell types
Types of stem cells; what are pluripotent cells and their function?
-Totipotent cells develop into pluripotent cells in embryos
-Are able to divide in unlimited numbers & produce any type of cell that makes up body
-Can be used to treat human disorders
Types of stem cells; what are multipotent cells and their function?
-Found in mature mammals
-Can develop into a limited number of cell types
Types of stem cells; what are unipotent cells and their function?
-Found in mature mammals
-Can divide to produce new cells but can only produce one type of cell
What is the process of stem cells becoming specialised?
-Totipotent cells become specialised in embryonic development
-When become specialised—> only some genes in cell are activated; those are expressed
-If gene is expressed—> transcribed into mRNA & translated into a protein
-Differentiation happens as certain proteins are made
-Presence of certain proteins= cell has become specialised
What are the 3 main sources of stem cells?
-Adult stem cells (taken from adult body tissues)
-Embryonic stem cells (taken from embryos)
-Induced pluripotent stem cells (iPS)
What are the benefits of using stem cells in disease?
-Can be used to reduce preventable deaths
-Can be used to treat conditions decreasing quality of life
What are the disadvantages of using stem cells?
-Obtaining them from embryos is controversial for ethical reasons; some think it is depriving an embryo of life
What are Induced Pluripotent Stem Cells (iPS) produced from?
-From a specialised adult somatic (body) cell
-Somatic cells → specialised, can’t be used to treat disease
How are iPS cells produced?
-Somatic cells are converted → iPS cells by activating genes using appropriate protein transcription factors
-Makes somatic cells unspecialised, so can treat disease
-Can be made from patient’s own body cells → decreases chance of rejection during transplants
How are stem cells used in bone marrow transplants?
-Transplants are used to treat blood & immune disorders
-Bone marrow has multipotent stem cells → can produce all types of blood cell
How are stem cells used in drug research?
-Stem cells are used to grow artificial tissues
-Drugs can be tested on the tissues before on humans
How can stem cells be used in developmental biology?
-Stem cells used to learn more about how an embryo develops & organs are formed
-Learning about developmental biology can help improve medicine by informing us why organs fail/have abnormalities
How can stem cells be used in potential future research?
-Stem cells can be used to make new organs/tissue from transplants
-Can also be used to treat irreversible diseases (eg paralysis)
-Could be injected at site of disorder/ problem & encouraged to differentiate → required specialised cell
What is gene expression controlled by?
Transcription factors
What are transcription factors and their function?
-Proteins that control gene expression by stimulating/ inhibiting transcription of target genes
-Are made in the cytoplasm & move to nucleus; here, they bind to a specific region of DNA to stimulate/ inhibit gene
What are activators and their function?
-Transcription factors that stimulate gene expression
-Promote transcription of genes by interacting w/ enzyme RNA polymerase, allowing it to bind to DNA
What are repressors and their function?
-Transcription factors that inhibit gene expression
-Prevent transcription of genes by stopping RNA polymerase from binding to DNA
What are the 2 hormones that can regulate transcription?
-Peptide hormones
-Lipid-soluble steroid hormones
How do peptide hormones regulate transcription?
-Bind to cell surface membranes, trigger secondary messenger response
-Secondary messenger leads to activation/ inhibitation of transcription of some genes
How do lipid-soluble steroid hormones regulate transcription + example of this?
-Can pass through phospholipid membrane
-Interact directly w/ DNA to promote/ inhibit gene expression
-Eg; oestrogen
What is the process of oestrogen initiating gene transcription?
-Oestrogen enters cytoplasm of cell through cell surface membrane; it is lipid-soluble so can pass through phospholipid bilayer
-Binds to receptors on transcription factors in cytoplasm; they change shape
-Transcription factors form receptor-hormone complex, can now enter nucleus
-The complex binds to promoter region of DNA; activates transcription & stimulates protein synthesis
What does epigenetic regulation do and what is the impact of this?
-Interacts w/ DNA to control access to DNA → alters gene expression w/out actually changing DNA code. Changes can be inherited
How is the chromatin formed and what surrounds it?
-DNA in nucleus combines w/ histone proteins → combination = chromatin
-Chemical layer surrounds chromatin → epigenome
What effect does the Epigenome have on the chromatin?
-Epigenome interacts w/ chromatin, changes its structure
-Can cause chromatin to become either: more condensed; prevents transcription factors from binding to DNA so transcription is inhibited or less condensed; allows easier access to transcription factors, promoting transcription
What are epigenetic markers and their function?
-Epigenetic markers= groups (e.g. methyl groups) that don’t alter base sequence but influence chromatin structure
-Chromatin becomes more/less condensed when epigenetic markers are attached/removed to DNA/histone proteins
What happens when there’s increased methylation?
-Methyl groups bind to CpG site (areas in DNA where cytosine & guanine are together in base sequence) on DNA
-Methyl groups cause chromatin to be more condensed; transcription factors can’t reach DNA
-Methylation inhibits transcription
What happens when there’s decreased methylation?
-Acetyl groups (CH3CO) are removed from histone proteins; increases their positive charge & so attraction to phosphate groups on DNA
-Decreased acetylation causes chromatin to condense; transcription factors can’t reach DNA
How do epigenetic markers influence inheritance?
-Action of epigenetic markers results in changes in chromatin structure
-Epigenetic markers can be inherited by offspring
-Inheritance of epigenetic control means environmental factors (e.g. methylation) experienced by individual can influence gene expression of offspring
When can epigenetics cause disease?
If they aren’t controlled properly
Epigenetics; how can abnormal methylation cause disease?
-Epigenetic changes can cause diseases (e.g cancer)
-Methyl groups are important in regulating processes like cell division
-If methylation isn’t regulated properly, can affect regulation of these important processes
Epigenetics; how can increased methylation cause disease?
-Can decrease gene expression of tumour suppressor genes more than normal
-Tumour suppressor genes prevent cell division from taking place
-If genes are underexpressed, cells divide uncontrollably & tumours are produced
Epigenetics; how can decreased methylation cause disease?
-Can increase gene expression of proto-oncogenes (which promote cell division) more than normal
-If genes are overexpressed, cells divide uncontrollably & tumours are produced
Why can epigenetics treat disease?
Epigenetic markers can be removed easily
How can epigenetics change treat disease and how does this impact drugs and therapies?
-Epigenetic changes that cause disease (e.g methylation leading to cancer) = temporary, can be reversed
-Ability to reverse epigenetic change= important for designing new drugs + therapies
-Researchers are investigating how drugs can reverse silencing/overexpression of genes
-Drugs that can reverse epigenetics can help return gene expression to normal level
What is translation inhibited by?
RNA interference (RNAi), small molecules of double-stranded RNA
How does RNAi influence gene expression?
Interferes w/ mRNA by binding to mRNA molecule, breaking it down; prevents it from being translated into protein
What is siRNA and its function?
-Type of RNAi complementary to mRNA sequence it inhibits
-Targets specific sequence of mRNA
-After siRNA has bound to mRNA, the mRNA is broken down into smaller fragments; which are degraded
What is miRNA and its function?
-Not fully complementary to mRNA sequence
-Can target multiple sequences of mRNA
-After miRNA has bound to mRNA, the mRNA is degraded or stored for future use
What do investigations into gene expression provide data on?
Which genes are ‘switched on’ & which genes are ‘switched off’
What are DNA microarrays used for?
-Measure gene expression
-Used to study extent to which certain genes are expressed in a cell
What are tumours and their two types?
-A cluster of cells growing uncontrollably. In some cases, can cause cancer
-Benign tumours
-Malignant tumours
What are the differences between benign and malignant tumours?
-Benign tumours: not cancerous, consist of cells dividing uncontrollably but cannot spread & invade other tissues. Can develop into malignant tumours
-Malignant tumours; cancerous, consist of cells dividing uncontrollably & spread into other tissues + around body. Can be life-threatening, grow rapidly
When do tumours develop?
When gene expression is not regulated correctly
What are tumor suppressor genes and how does their inhibition cause the development of tumours?
-Genes found in all cells; inhibit cell division to regulate rate at which cells divide
-Increased methylation of a tumour suppressor gene inhibits this gene; when tumour suppressor genes aren’t expressed, cell division isn’t inhibited: cells divide uncontrollably
What are oncogenes and how can they cause development of tumours?
-Mutations in a gene called a proto-oncogene
-Are capable of transforming cell into cancerous cell as they cause excessive cell division
-Proto-oncogenes normally stimulate cell division; decreased methylation of them causes proto-oncogenes to be over-expressed: stimulates cell division
How can oestrogen cause the development of tumours?
-Can increase expression of genes; when they’re over-expressed, a tumour may develop
-High levels of oestrogen have been detected in some breast cancers.
What are the two factors affecting the development of cancers + examples?
-Environmental factors, including exposure to radiation, smoking, alcohol consumption, eating a diet high in fat
-Genetic factors, including having certain alleles
What is correlation vs causation in factors affecting the development of cancer?
-Environmental & genetic factors have been found to correlate w/ cancer
-Correlations= there’s an association between the two factors
-Correlations are different from causes as they don’t always mean a person will develop cancer
How can information related to the roles of oncogenes & tumour suppressor genes be used to prevent cancer?
-Understanding what increases chance of creating mutations in oncogenes & tumour suppressor genes (e.g. radiation) can help prevent cancer
-Preventative measures can be taken; will reduce the risk of developing cancer
-More sensitive tests can be used to diagnose cancers
How can information related to the roles of oncogenes & tumour suppressor genes be used to treat cancer?
-If we know what gene mutations cause cancer, drugs can be developed to target these specific mutations
-Treatment for cancer can be made more specific by differing drugs according to type of mutation
-Intensity of treatment needed can be determined by identifying what mutation= cause
-Some mutations are more aggressive, require stronger treatment than others
