Regulating Gene Expression

-Can be controlled at the transcriptional, post-transcription and post-translational level

- gene expression controlled by transcriptional level by altering the rate of transcription of genes

- controlled by transcription factors - proteins that bind to DNA and switch genes on or off by increasing and decreasing the rate of transcription. factors that increase the rate are called ACTIVATORS and factors that decrease the rate are called REPRESSORS.

- the shape of a transcription factor determines whether it can bind to DNA or not and can sometimes be altered by the binding of some molecules. 

- this means the amount of certain molecules in an environment or a cell can control the synthesis of some proteins by affecting transcription factor binding.

- in eukaryotes, transcription factors bind to specific DNA sites near the start of their target genes, the genes they control the expression of.

- in prokaryotes control of gene expression involves transcription factors binding to operons

- a section of DNA that contains a cluster of structural genes, that are transcribed together, as well as control elements and sometimes a regulatory gene:

- the structural genes code for useful proteins, such as enzymes

- the control elements include a promoter (a DNA sequence located before the structural genes that RNA polymerase binds to) and an operator (a DNA sequence that transcription factors bind to)

- The regulatory gene codes for an activator or repressor

- E. coli is a bacteria that respires glucose but can use lactose if glucose is not available.

- genes that produce the enzymes needed to respire lactose are found on an operon called the lac operon

- the lac operon has 3 structural genes - lacZ, lacY, and lacA, which produce proteins that help the bacteria digest lactose (including beta-galactosidase and lactose permease)

WHEN LACTOSE IS NOT PRESENT

- the regulatory gene produces the lac repressor, which is a transcription factor that binds to the operator site when theres no lactose present. this blocks transcription because RNA polymerase cant bind to the promoter. 

WHEN LACTOSE IS PRESENT

- it binds to the repressor, changing the repressor's shape so that it can no longer bind to the operator site. RNA polymerase can now begin transcription of the structural genes.

- genes in eukaryotic DNA contain sections that dont code for amino acids

- these sections of DNA are called INTRONS. all the bits that do code for amino acids are called EXONS.

- during transcription the introns and exons are both copied into mRNA. mRNA strands containing introns and exons are called primary mRNA transcripts (or pre mRNA)

- introns are removed from primary mRNA strands by process called SPLICING - introns are removed and exons are joined, forming mature mRNA strands. takes place in nucleus.

- the mature mRNA the leaves the nucleus for translation

-cAMP activates some proteins at post transcriptional level

- some proteins arent functional after they have been synthesised so they need to be activated to work

- protein activation is controlled be molecules eg: hormones and sugars

- some of these molecules work by binding to cell membranes and triggering the production of cAMP inside the cell

- cAMP then activates proteins inside the side by altering the 3D structure

-eg: altering the 3D structure can change the active site of an enzyme, making it become more or less active

HOW CAMP ACTIVATES PKA

-PKA is enzyme made of 4 subunits, when cAMP not bound the 4 units are bound together and are inactive, when cAMP binds it causes a change is the enzymes 3D structure releasing the active subunits - PKA is now active.

- Body plan is general structure of an organism, that are arranged in a particular way

- proteins control development of body plan - help set up basic body plan so everything is in the right place

- proteins that control body plan development are coded for by genes called Hox genes

- hox genes found in flies, mice, humans etc. have regions called homeobox sequences which are highly conserved - this means that sequences have changed very little during the evolution of different organisms that possess these homeobox sequences

HOW HOX GENES CONTROL DEVELOPMENT

- homeobox sequences code for part of the protein called the homeodomain

- the homeodomain binds to specific sites on DNA enabling the protein to work as a transcription factor

- the proteins bind to DNA at the start of developmental genes, activating or repressing transcription and so altering the production of proteins involved in development of body plans.

- programmed cell death

HOW THE CELL IS BROKEN DOWN:

1. enzymes inside the cell break down important cell components such as proteins in cytoplasm and DNA in nucleus

2. as the cell contents are broken down it begins to shrink and breaks up into fragments

3. the cell fragements are engulfed by phagocytes and digested.

- cell divides to form 2 daughter cells

- mitosis and differentiation create the bulk of the body parts then apoptosis refines the parts by removing the unwanted structures. 

- eg: when humans hands and feet are developed the fingers and toes are connected so are only separated when cells in the connecting tissue undergo apoptosis

- during development, genes that control mitosis and apoptosis are switched on and off in appropriate cells. this means some cells die, whilst some new cells are produced and the correct body plan develops. 

- genes that regulate apoptosis and progression through the cell cycle can respond to both internal and external stimuli

- internal stimulus could be DNA damage. if DNA damage is detected during the cell cycle this can result in the expression of genes which cause the cell cycle to be paused and even trigger apoptosis.

- an external stimulus such as stress caused my lack of nutrient availability, could result in gene expression that prevents cells from undergoing mitosis. gene expression which leads to apoptosis being triggered can also be caused by an external stimulus such as attack by a pathogen. 

- SUBSTITUTION - one or more bases are swapped for another eg: ATGCCT becomes ATTCCT

- DELETION - one or more bases removed eg: ATGCCT becomes ATCT

- INSERTION  - one or more bases added eg: ATGCCT becomes ATGACCT

- the order of DNA bases in a gene determines the order of amino acids in a particular protein. if a mutation occurs in a gene then the primary structure of the protein it codes for could be altered. 

- this may change the final 3D shape of the protein so it doesnt work properly eg: active sites in enzyme may not form properly. 

- NEUTRAL - mutation changes base in a triplet but amino acid coded for doesnt change, happens because some amino acids are coded for by more than 1 triplet. the mutation codes for a different amino acid that is chemically similar to the original so functions like original. mutated triplet codes for an amino acid not involved with the proteins function. - wont effect organism overall

- BENEFICIAL - have advantage effect on an organism eg: increase chance of survival. some bacterial enzymes break down antibiotics, mutations in the genes codes for enzymes that break down wider range of anitbiotics so bacteria able to survive.

- HARMFUL - have disadvantage effect on an organism eg: decrease its chance of survival. cystic fibrosis can be caused by deletion of 3 bases that codes for the CFTR protein. the mutated CFTR protein folds incorrectly so its broken down which leads to excess mucus production which affects the lungs of CF sufferers. 

- mutations can also affect whether or not a protein is produced, the loss of production of a protein may have harmful effects.