8.2 gene expression is controlled by a number of features

what is a totipotent cell?

Undifferentiated cells which have the ability to divide continuously and mature into any type of body cell

what is a pluripotent cell?

Can divide in unlimited numbers cells and have the ability to give rise to several cell types

what is a multipotent cell?

Cells which have the ability to divide and give rise to a limited number of cell types (fewer than pluripotent cells)

what is a unipotent cell?

Cells which can only divide to form one type of cell

what is an induced pluripotent stem cell (iPS cell)?

Pluripotent cells which are produced by treating unipotent cells with specific protein transcription factors

what is a stem cell?

Undifferentiated cells which can divide continually and can differentiate into any type of cell

how are iPS stem cells produced?

4 protein transcription factors are added to unipotent cells (called ‘Yamanaka factors’) and this causes the cells to turn back into pluripotent cells

suggest why injecting embryonic stem cells into someone to treat a disorder could cause harm

• The cells could differentiate into the wrong cell types

• The cells could divide out of control, leading to formation of a tumour and possibly cancer

what is a transcription factor?

• A Transcription factor binds to a gene

• At a specific DNA sequence in the promoter;

• Stimulates RNA polymerase to attach and transcribe the gene (or can prevent transcription)

how would a transcription factor increase the production of a protein?

• The transcription factor will move from the cytoplasm of the cell to the nucleus

• The transcription factor will bind to the promotor region of a gene

• This will cause RNA polymerase to attach and stimulate transcription to take place

• Therefore, more of the protein will be produced

what is oestrogen?

A steroid hormone

how does oestrogen affect gene transcription?

• Oestrogen binds to the oestrogen receptor (which is found in the cytoplasm)

• This causes the oestrogen receptor to change shape and an inhibitor molecule is released

• This exposes the DNA binding site on the oestrogen receptor

• The oestrogen receptor complex moves into the nucleus via the nuclear pore

• And binds to the specific base sequence in the promotor region of a gene

• This stimulates RNA polymerase to attach and transcription to take place

what is the function of RNAi?

RNA molecules (such as siRNA or microRNA) inhibit gene expression by ‘neutralising’ specific

mRNA molecules so that translation cannot take place.

They bind to complementary mRNA sequences either preventing the mRNA from attaching

to the ribosome or enabling enzymes to break up the mRNA

how does RNAi function?

1. Double stranded RNA is produced

2. Leaves the nucleus

3. One strand of RNAi is bound to RISC, which is a complex with proteins (including RNA hydrolase)

4. The RNAi guides the enzyme to mRNA that has a complementary sequence of bases.

5. The RNAi binds to the mRNA by complementary base pairing

EITHER

• The enzyme cleaves the mRNA into pieces

OR

• The mRNA is blocked from binding to a ribosome

So either way:

• translation is prevented

what is epigenetics?

The study of heritable changes in gene function that do not involve changes to their base sequences

what is DNA methylation?

The addition of methyl groups to DNA bases (usually to cytosine).

describe and explain the effect of increased DNA methylation on gene expression

• Increased methylation of DNA in the promoter region of a gene will prevent transcription factors and RNA polymerase from binding

• Transcription of the gene will be inhibited and the gene will be ‘silenced’

what are histones?

The proteins that DNA is wrapped around

what is histone acetylation?

The addition of acetyl groups to histone proteins.

describe and explain the effect of histone acetylation on gene expression

• Histone acetylation causes DNA to be less condensed;

• Which can reveal the promoter regions of the genes;

• Which can lead to increase binding of transcription factors and RNA polymerase to the

promoter regions;

• Which can lead to increase transcription of the gene

what are the main characteristics of a benign tumour?

A mass of dividing cells which do not break away and invade neighbouring tissue (i.e, do not metastasise)

what are the main characteristics of a malignant tumour?

A mass of cells which divide uncontrollably and can metastasise, invading other tissues

what does an oncogene do?

It codes for a protein which stimulates cell division to take place

what is the consequence of a mutation occurring to an oncogene?

• Change in base sequence of DNA

• Change in primary structure of protein (sequence of amino acids)

• So change in tertiary structure of protein

• This results in uncontrollable cell division.

what does a tumour suppressor gene do?

It codes for a protein which prevents cell division from taking place

what is the consequence of a mutation occurring to a tumour suppressor gene?

• Change in base sequence of DNA

• Change in primary structure of protein (sequence of amino acids)

• So change in tertiary structure of protein

• The tumour suppressor gene becomes inactivated

Results in uncontrollable cell division

how can abnormal methylation of a tumour suppressor gene lead to the development of a tumour?

• Increased methylation / hypermethylation of DNA in the promoter region of a gene will prevent transcription factors and RNA polymerase from binding

• Transcription of the gene will be inhibited and the gene will be ‘silenced’

• So less of the tumour suppressor protein will be produced

• So mitosis can no longer be stopped

• So there is uncontrollable cell division

how can abnormal methylation of an oncogene lead to the development of a tumour?

• Decreased methylation / hypomethylation of DNA in the promoter region of a gene will

allow transcription factors and RNA polymerase to bind

• So more of the oncogene protein will be produced

• So rate of mitosis increases

• So there is uncontrollable cell division

suggest how increased oestrogen concentration can lead to development of some breast cancers?

• Oestrogen binds to oestrogen receptors

• So the tertiary structure of the oestrogen receptor changes, so that the DNA binding

site is exposed

• The oestrogen receptor binds to promoter of an oncogene

• This allows RNA polymerase to bind and causes transcription to occur

• more of the protein will be produced → uncontrollable cell division

explain how the methylation of tumour suppressor genes can lead to cancer. (3)

• tumour suppressor genes in not transcribed

• so no tumour suppressor gene present

• so uncontrolled cell division

describe how alterations to tumour suppressor genes can lead to the development of tumours. (3)

• methylation of tumour suppressor gene

• Z so not transcribed

• so no tumour suppressor genes created

• so uncontrolled cell division

suggest how transcription factors can reprogramme cells to form iPS cells. (2)

• 4 transcription factors bind to promoter region on unipotent stem cell

• so RNA polymerase stimulated