control of gene expression

Does every cell have the same genotype in humans?

yes

Why is gene expression regulated?

• Cells express only genes needed for their function

• amount of Protein vary with cell type and cell cycle stage

• Making proteins uses lots of energy, so unnecessary synthesis is avoided

When is gene expression regulated?

• during differentiation

• during development 

• as a ressponse to environemnt 

• depending on the function of the cell

what are the stages of gene expression and when can it be regulated 

1. DNA is unfolded from histones to make genes accessible

2. Transcription factors bind and start transcription (DNA → mRNA)

3. mRNA is processed (splicing, capping, poly-A tail added)

4. Translation factors help make protein from mRNA

5. Protein modified or broken down after it’s made

What are the 2 levels at which gene expression can be regulated?

Epigenetics and transcriptional regulation

What is epigenetics and transcriptional regulation?

• epigenetics changes gene activity and expression without changing the DNA sequence, 

• transcriptional regulation controls when and how much a gene is transcribed into RNA.

why do epigentic factors affect chromatin and not  DNA sequence

epigenetic factors mean changing in gene activity without changing DNA sequence


epigenetic factors change how tightly  the DNA is wrapped around the histone the more tighter packed ( heterchromatin) makes the gene less transcriptionally active the more loosley packed ( euchromatin) makes the gene more trancriptionally active 

What is a nucleosome

8 histones + DNA wrapped around it
1 unit of chromatin

what chemical changes make epigenetic code 

• it controlls whether a gene is swithced on or off

• DNA methylation – addition of methyl groups (–CH₃) to cytosine bases in DNA

• Histone modification – addition or removal of chemical groups (like acetyl, methyl, or phosphate) to histone proteins

How are histone tails modified  and what does it cause

• Histones have N-terminal tails that stick out from the nucleosome.

• These tails can be chemically modified by acetylation ( add acetyl group)  methylation ( add methyl group ) , or phosphorylation ( add phosphate group ).

• The modifications change chromatin condensation, affecting how tightly DNA is wrapped around histones.

• This alters DNA accessibility, making genes easier or harder to transcribe.

• Through these changes, cells can switch large regions of chromosomes on or off, allowing global gene regulation.

How does DNA methylation workAKA cytosine methylation 

• Where: Occurs at CpG sites (cytosine next to guanine).

• What happens: An enzyme called DNA methyltransferase (DNMT) adds a methyl group (–CH₃) to the cytosine base.

• Effect:

  • Prevents transcription factors from binding.

  • Attracts proteins that condense chromatin, making DNA tightly packed (heterochromatin).

• Result: The gene is silenced (turned off) — less or no mRNA is made.

• Reversible: Methyl groups can be removed (demethylation), allowing gene reactivation.

What is dual inheritance?

• organism inherit genes in ways: 

1. Genetic inheritance: genes passed from parent to offspring.

2. Epigenetic inheritance: chemical tags or chromatin marks (like DNA methylation, histone modification) that control how those genes are expressed, not the genes themselves.

How is epigenetics and disease linked?

• chemical changes to DNA or histones can turn genes on or off without changing the DNA sequence ( methylation, histone ,modification)

• these changes can be influenced by the environment and sometimes passed to offspring, affecting their risk of disease.

How can problems with gene expression cause cancer?

The absence of transcription off switch leads to the wrong genes being expressed and it causes cell division

How can problems with gene expression cause chronic diseases (e.g obesity)?

Abnormal gene expression because of the wrong signals in the

cell can cause inflammation and increased risk of other diseases

How can problems with gene expression cause developmental diseases?

Mistakes in early protein synthesis can lead to organ developmental problems

What external stimulus can alter gene expression?

Exposure to toxins or drugs

how and by what is transcription initiation controlled 

• a regulatory protein control how much and wen a gene is transcibed 

• they have to binding sites the DNA binding domain and a transcription activation domain, that attach to the DNA 

• the regulatory protein is made in the cell and diffuses to the nucleas and binds to th DNA it either allows or blocks RNA polymerease 

What is needed for transcription initiation?

General transcription factors (GTFs)

what are the 2 types of regulatory sequences and explain

1. cis- they influence genes on the same molecule of DNA 

2. trans - act on other DNA molecules to regulate gene expression.

Where are regulatory sequences found in the genome?

the non-coding regions of the genome

what is the differnce between regulatory sequences and regulatory proteins

• Regulatory sequences are DNA regions (like promoters, enhancers, silencers) that control gene expression.

• Regulatory proteins (like transcription factors) are proteins that bind to these DNA sequences to turn genes on or off.

What do regulatory sequences do?

they interact with DNA binding proteins e.g. transcription factors resulting in induction or repression of transcription initiation

What is the TATA box?

a DNA sequence in eukaryotic promoters in the 5' region that helps form the transcription initiation complex, allowing RNA polymerase II to start transcription.

What happens if transcription initiation goes wrong?

• if the sequence is missing to switch the gene off and you keep expressing a protein which is going to lead to cell growth and cancer

How is gene expression regulated by hormones?

hormones bind to receptors which can switch genes on or off

some hormones can enter the cell making a hromon-receptor complex which can move to the nucleas and bind to DNA

What are 2 ways that mRNA processing is regulated?

Polyadenylation (rare) and splicing (common)

how is polyadenylation regulated

• normally the poly A tail is added 

• but U1A is a protein that binds just before the polyA site 

• U1A bidns to its own mRNA which means it stops translation down stream also stopping the translation that woudl of made the poly A tail 

• this is negatuve feedback so when there alot fo U1a protein then it stops makig more as the mRNA is blocked 

• if there is low u1A then not much mRNA is blcoked so it cna make more

what is splicing and alternative splicing

• introns removed by splicing

• alternative splicing can remove specific exons

Explain alternative splicing in gene regulationusing the example of fibronectin

• liver and fibroblast make fibronectin but the protein they make has different properties because of alternative splicing

• liver makes soluble fibronectin for clotting 

• fibroblast make insolube fibronecting for tissue structure

regulation of protein synthesis summary

  1.    Epigenetic level – DNA accessibility (chromatin structure)

- doesnt change the DNA sequence only the activity 
- it affects chromatin not DNA sequence 
- heterochromatin ( tighter) - gene offf 
- euchromatin (looser) - gene on 

how?

1. DNA methylation → adds –CH₃ to cytosine → gene off
2. histone modification →  acetyl, methyl, phosphate groups change how tightly DNA wraps → controls transcription


       2.   Transcriptional level – control of mRNA production

- controlled by regulatory proteins ( transciption factors) 
- transcription factors have a DNA binding domain and a activation domain 
- trancription factors bind to regulatory sequences which are found in the non coding region ( e.g promoters) 
- cis- the transcption factor acts on the same DNA strand 
- trans- the transcription factor acts on another DNA molecule
-TATA box where the RNA polymerease binds 


     3.   Post-transcriptional – splicing, capping, poly-A tail

-polyandylation:  added to ther 3' end and it helps mrna go to translation but when there U1A protein this is just before the poly A tail and it binds to its own mRNA stopping translation of the poly A tail 

splicing: remove introns 
alternative splicing: remove certain exons 

capping: 
cap added to 5' end this stabalised the mrna moving it to be translated 

    4.   Translational – control of protein synthesis

- controls how much protein is made from mRNA 

   5.  Post-translational – protein modification or breakdown


hormone control: 
- hormones bind ot receptors 
- some hormones eneter the cell making a hormon-receptor complex which canbidn to dna switching genes on/off