BIO; Gene expression is controlled by a number of features

what are stem cells

undifferentiated cells that can continually divide

and differentiate to become specialised

what are the different types of stem cells

totipotent

pluripotent

multipotent

unipotent

what are totipotent stem cells

can divide and produce any type of body cell;

occur for a limited amount of time

what are pluripotent stem cells

found in embryos;

can become almost any type of cell (not the placenta)

used in research to treat human disorders;

e.g. regrow damaged cells like replace burnt skin cells, beta cells for type 1 diabetes etc

whats the issues with using pluripotent stem cells

• can continually divide to create tumours

• need to make a therapeutic clone of oneself to make an embryo to obtain stem cells (is it ethically moral? bc embryo used is later destroyed)

what are multipotent stem cells

found in mature mammals;

divide to form a limited number of different cell types

example of a multi potent cell; bone marrow cells

what are unipotent stem cells

found in mature mammals;

only differentiate into one type of cell

e.g. cardiomyocytes are unipotent stem cells which regenerate new heart muscle cells in small numbers

what are induced pluripotent stem cells (iPS cells)

produced from adult body cells using appropriate transcription factors;

ensuring all genes can be transcribed again, making them pluripotent in property (can differentiate into almost any cell type)

helps overcome the ethical issues when using embryonic stem cells — bc a cloned embryo is not made so no embryo is later destroyed

how are induced pluripotent stem cells(iPS cells) made

1. iPS cells are made from adult unipotent cells

2. adult unipotent cells are altered in a lab to return them to state of pluripotency

3. genes that were switched off to make the cell specialised must be switched back on

4. done using transcriptional factors

how are induced pluripotent stem (iPS) cells more ethical than embryonic pluripotent stem cells

• iPS cells do not need to create a clone of the embryo, so doesn’t cause the destruction of an embryo

• and adults can give permission

• iPS cells have a self-renewal property - can give limitless supplies so can be used in medical treatment

how do transcription factors work

transcription of a gene can only occur;

1. when a transcription factor from the cytoplasm enters the nucleus

2. and binds to the promotor region on DNA in the nucleus

3. each one can bind to a different base sequence on DNA

4. then it stimulates RNA polymerase so transcription begins

5. creating mRNA for translation in the cytoplasm

!!! without the binding of a transcription factor - the gene is INACTIVE so protein can’t be made

how does oestrogen activate transcription factors (TF)

oestrogen is a lipid soluble steroid hormone (can diffuse through cell membrane via simple diffusion);

1. inside cytoplasm of cell, oestrogen binds to a receptor (complimentary in shape) on the TF

2. this alters the tertiary shape of the TF

3. this changes the DNA binding site, so now complimentary in shape to a particular sequence of DNA bases

4. which activates the TF

5. activated TF moves into nucleus

6. and binds to specific DNA sequences in promotor region of a target gene (has specific DNA base sequence complimentary to DNA binding site on TF)

7. stimulating RNA polymerase to bind

8. transcription occurs

how can gene expression be controlled in eukaryotic organisms

by epigenetics

what are epigenetics (2 MARKS)

• heritable change in gene function,

• without changing the DNA base sequence;

these changes are caused by changes in the environment (stress/diet)

and can inhibit/initiate transcription

how is transcription controlled

acetylation of histones

methylation of DNA

whats the impact of increased methylation of DNA

1. when methyl groups are added to DNA they attach to cytosine base;

2. causes DNA-histone complexes to pack tightly together

3. so transcriptional factors can’t reach the genes to bind

4. preventing transcriptional factors from binding

5. so RNA polymerase can’t be stimulated

6. so transcription is inhibited

whats the impact of increased acetylation of histone proteins

-initiates transcription;

1. acetyl group is partially negative bc of the oxygen on it

2. DNA also has a partial negative charge bc of its phosphate group

3. this causes them to repel eachother

4. so DNA-histone complexes are loosely packed

5. makes DNA accessible for transcriptional factors to bind to the promotor region of the DNA

6. stimulating RNA polymerase

impact of decreased acetylation of histone proteins

inhibits transcription;

1. histones become more positive

2. so are attracted more to the negative phosphate group on DNA

3. makes the DNA-histone complexes pack together tightly

4. DNA becomes inaccessible

5. prevents transcription factors to bind to promotor region of DNA

6. RNA polymerase is not stimulated

how is translation of mRNA inhibited (siRNA pathway)

via RNA interference and small interfering RNA;

1. siRNA is produced from double stranded RNA

2. and splits into a single strand

3. single strand of siRNA binds to a protein

4. making a protein complex

5. one strand of the siRNA binds to a complimentary sequence of a mRNA

6. mRNA and siRNA are bound in the protein complex

7. this binding causes an enzyme to cut the mRNA

8. preventing translation of mRNA

how is translation of mRNA inhibited (miRNA pathway)

1. microRNA (miRNA) not fully complimentary to its target mRNA

2. so binds to multiple mRNA molecules

3. blocking ribosome attachment

4. results in gene silencing at translation

how is a cancer formed from mutations

cancer results from mutations in genes that regulate mitosis;

if this gene mutates and non functioning proteins are made,

then mitosis is not regulated

results in uncontrollable division of cells (tumour)

describe benign tumours

• grow very large but at a slow rate;

• non cancerous - they produce adhesive molecules sticking them together to a particular tissue

• surrounded by capsule - remain compact and can be removed by surgery

• the impact is localised - in a capsule so won’t break away (stays intact)

describe malignant tumours

• cancerous - doesnt produce adhesive, so instead metastasise (breaks off and spreads)

• grow rapidly

• cell nucleus grows large

• and becomes unspecialised

• not encapsulated - grow into surrounding tissues

• and develops its own blood supply

how can tumours develop

due to gene mutations in;

tumour supressor gene

oncogene

what are oncogenes

mutated version of proto-oncogene (creates a protein for the initiation of DNA replication & mitosis)

oncogene mutations can result in DNA replication and mitosis being permanently activated — cells divide continuously

what are tumour suppressor genes

genes that produce proteins to slow down cell division and cause cell death;

!!! mutation - tumour suppressor gene cannot produce proteins to slowdown cell division and mutated cells cannot be destroyed

how does methylation impact cancer

methylation can cause a gene to turn on/off

• tumour suppressor genes become hypermethylated;

increased number of methyl groups attached to it (results gene being inactivated)

cell division is not slowed down

• oncogenes become hypomethylated;

reduced number of methyl groups attached

(results in gene being permanently switched on)

cells divide continuously

how is the risk of breast cancer increased after menopause

oestrogen is no longer produced in ovaries but instead produced by fat cells in breast tissue;

1.oestrogen binds to receptor proteins within target cells

2. forming a complex that acts as a transcription factor

3. complex binds to specific DNA sites to stimulate transcription

4. if oestrogen stimulates transcription of a photo-oncogene, may cause that gene to be over transcribed

5. results in the protein that stimulates cell division, to be produced in large numbers

6. creates a positive feedback loop