8.2 Gene expression is controlled by a number of features Flashcards
What are stem cells?
Unspecialised cells capable of:
Self-renewal; can divide to replace themselves
Specialisation/differentiation; can develop into other types of cell
Define totipotent:
Has the ability to give rise to all cell types eg/ fertilised egg/zygote
Define pluripotent:
Found in embryos. Can differentiate into almost any type of cell
Define multipotent:
Found in adults/mature mammals. Differentiate into a limited number of specialised calls eg/ blood stem cells in bone marrow umbilical cord
Define unipotent:
Found in adults/mature mammals can only differentiate into a single type of cell. Derived from multipotent and made in adult tissue
Describe the process of stem cell specialisation
- Stimulus eg/ chemical
- Causes selective activation of genes - some genes activated while others inactivated (eg/ muscle cell genes coding for actin and myosin need to be activated)
- mRNA only transcribed from active genes -> translated on ribosomes = proteins
- These proteins modify cell permanently and determine cell structure/function
How can pluripotent stem cells be used in medicine?
They can divide in unlimited numbers
- Regrow damaged tissues in accidents (i.e. skin grafts) or by disease (i.e. neuro-degernerative diseases, Parkinson’s disease)
- Drug testing - used to grow artificial tissues
- Developmental biology research - provide insight into embryological development
How are induced pluripotent stem cells produced?
- Produced from adult somatic cells
- Specific protein transcription factors associated with pluripotency put into cells, causing the cell to express genes associated with pluripotency
- Cells cultured
- = Induced pluripotent stem cells
How are induced pluripotent stem cells used in medical treatment instead of embryonic cells?
- No immune rejection as can be made using patient’s own cells
- Overcome some ethical issues with using embryonic stem cells eg/ no destruction of embryo and adult can give permission
Evaluate the use of stem cells in treating human disorders:
For:
Use of embryonic stem cells
- Tiny ball of cells, incapable of feeling pain, not equivalent to a human
- Would otherwise be destroyed (if from infertility treatment which creates more than needed)
Duty to apply knowledge to relieve human suffering
Against:
Use of embryonic stem cells
- Embryo is a potential human; should be given rights
Scientific
- Induced pluripotent stem cells - cannot yet reliably reprogramme stem cells
- Could begin to multiply out of control, and cause tumours
What are transcription factors:
- Transcription factors are proteins
- Move from cytoplasm -> nucleus
- Bind to DNA at a specific DNA base sequence on a promotor region
- Stimulate or inhibit transcription
Transcription -> mRNA -> translation -> polypeptide
What is the role of oestrogen in initiating transcription?
- Steroid hormone so is lipid soluble (can diffuse across the phospholipid bilayer of the cell-surface membrane)
- Binds with receptor molecule of transcription factor
- Causes conformational change in transcription factor protein (promoter region) and can now bind to DNA -> enters nucleus
- Binds to specific sequence on DNA and stimulates transcription
What are nucleosomes?
DNA wrapped around histone proteins
- How closely the DNA and histone are packed together affects transcription
Define epigenetics:
Environmental factors that can cause heritable changes in gene functions without changing the base sequence of DNA
- These changes are caused by changes in the environment that inhibit transcription
What is the epigenome?
- The chemical tags forming a second layer around DNA and histones
- It is flexible - chemical tags respond to environmental changes
- Accumulation of signals it has recieved during its lifetime
- Can activate or inhibit specific sets of genes
What happens when the DNA histone complex (chromatin) is loosely packed?
When loosely packed DNA is accessible by transcription factors. Gene is switched on
What happens when the DNA histone complex (chromatin) is tightly packed?
DNA not accessible therefore gene is switched off
What happens when the DNA histone complex (chromatin) condenses?
Condensation of DNA histone complex can inhibit transcription
Describe the methylation of DNA:
- Methyl groups added to cytosine bases in DNA
- Nucleosomes pack more tightly together -> prevents transcription factors binding; genes not transcribed (RNA polymerase can’t bind)
- Irreversible
- Attracts proteins that condense DNA-histone complex
Gene is switched off
Describe the deacetylation of DNA:
- Increases positive charges on histones
- Therefore increases the attraction to the phosphate groups of DNA
- Association of DNA and histone is stronger
- DNA is not accessible to transcribe
- Gene is switched off
How is epigenetics relevant to disease development and treatment? (esp cancer)
- Epigentic process can cause silencing of genes. This has been linked to a number of cancer types
- Also activating a normally silent gene can cause cancers
- Tests can be used to see if a patient has abnormal levels of methyl and acetyl - early indicator of cancer (biomarker)
- Could be manipulated to treat cancer
What is RNA interference (RNAi)?
-RNA molecules inhibit translation of mRNA produced by transcription
RNAi can be moderated by either siRNA/miRNA. What’s the difference?
Micro-RNA (miRNA):
- Formed as hair-pin bends of RNA but processed into single-strands 22-26 nucleotides long, both become incorporated into a protein-based RISC
Small interfering RNA (siRNA):
- Formed as double-stranded molecules 21-25 bp long, one strand incorporated into a protein-based RISC
RNAi can be moderated by either siRNA/miRNA. What’s the difference?
Micro-RNA (miRNA):
- Formed as hair-pin bends of RNA but processed into single-strands 22-26 nucleotides long, both become incorporated into a protein-based RISC
Small interfering RNA (siRNA):
- Formed as double-stranded molecules 21-25 bp long, one strand incorporated into a protein-based RISC
Describe the process of how a double-stranded RNA gets to small sections of mRNA:
- Double stranded RNA is broken up by an enzyme into small interfering RNA (siRNA)
- One of the two strands of siRNA combines with an enzyme
- The siRNA strand pairs with complementary bases on a mRNA strand
- The enzyme cuts the mRNA into smaller sections (stops a gene from being expressed)
Removing mRNA can essentially stop a gene from being expressed in eukaryotes and some prokaryote
When a proto-oncogene mutates into an oncogene it can become permanently activated (switched on) for two reasons, why?
- The receptor protein on the cell-surface membrane can be permanently activated, so that cell division is switched on even in the absence of growth factors
- The oncogene may code for a growth factor that is then produced in excessive amounts, stimulating excessive cell divison
What is the result of proto-oncogenes being permanently switched on?
The result is that cells divide too rapidly and out of control, and a tumour/cancer develops
What are tumour suppressor genes?
Tumour suppressor genes slow down cell division, repair mistakes in DNA and have programmed cell death (apoptosis).
Maintains normal rates of cell division and so prevents the formation of tumours
