Cell Differentiation, Determination & Senescence Flashcards
What is cell differentiation?
Production of different cell types within an organism
What is another name for a new expression pattern?
Program differentiation
Give an example of when modulation occurs?
The up regulation of alcohol dehydrogenase in hepatocytes
- when blood alcohol levels increase
Experimentally how is differential transcription detected?
Using individual probes or microarrays we can test 1000’s of unknown RNAs
- reveals any mRNA differences between 2 cell types
What is cell determination?
The stability of cell differentiation even after any inducing signal has been transmitted to daughter cells after division
What is De Novo methylation?
Unmethylated CpG pairs get methylated during differentiation and gamete formation by de Novo
methyltransferase enzyme
How does MTIF protein regulate transcription of genes?
MTIF gene undergoes transcription & translation -> MTIF protein
MTIF protein binds to program promoters activating them
Program genes are translated into specialised proteins
What is a cell lineage?
The developmental history of a differentiated cell from the zygote
Which sites on a gene can Transcription factors bind to in order to alter transcription
of that gene?
- Transcriptional Start site (TATA box - basal promoter)
- Promoter Region (motifs and sequences complementary to TF)
- Enhancers (3’ of gene or in introns)
What do the branches on cell lineage diagrams represent?
Branches represent the different cell types each precursor can differentiate into
Does not represent cell division!!!
What are Household genes?
Genes that are transcribed in (nearly) all cell types
Give an example of cell determination
Different types of Blood cells
- they’re all in the same environment but remember what cell type they all are
How do different TFs activate different genes?
Via the specific binding elements in their promoters and enhancers
Different cell types express different TFs, transcribing different sets of genes
What is the role of Master gene regulators?
Regulate transcription of a program for a given cell type
What can cause a change in gene expression?
- Mutations
- Differentiation
- Modulation
Compare the mRNA differences between skeletal muscle and melanocytes
Skeletal Muscle Protein mRNA
- muscle actin
- muscle creatine kinase
- myoglobin
Melanocytes Protein mRNAs
- Tyrosinase
- sopachrome
- tautomerase
- myosin 5a
What type of division pattern do Liver endothelium cells follow?
Liver endothelial cells divide very little but divide to repair any cell damage
Why do some cell lineages branch into different cell types?
When the precursors are pluripotent they differentiate into various cell types
How does methylation cause heterochromatin formation?
DNA methylation tends to occur in whole stretches of DNA rich in CpG pairs
methylated DNA becomes highly folded -> heterochromatin
Give examples of non lethal differentiation birth defects?
Aniridia
- lack of eye iris due to PAX6 mutation
Congenital Anaemia & thrombocytopenia
- Mutation of GATA1 TF responsible for erythrocyte and platelet differentiation
How does DNA Methylation occur?
Cytosine in a CpG pair is methylated
Methylation is copied to daughter strands (as copied to opposite strand)
methylation pattern is remembered in daughter cells
Name the 2 common examples of master gene regulators illustrating the positive feedback mechanism
- MITF in melanocytes
- MYOD1 in skeletal muscles
How does differentiation and modulation differ?
Differentiation: Stable, complex change
Modulation: Temporary, simple change
What are the 3 main division patterns of mature differentiated cells?
- Very little division but for repair damage
- Terminal differentiation - cells don’t divide
- Precursor division
What is the consequence of methylation?
Methylation of a gene , especially on a promoter, silences the gene
What is modulation?
A simple reversible change in gene expression dependent on a continuous external stimulus no
change to the cell type
What is MTIF?
Master regulator gene that forms a master regulator protein called MTIF protein
How is heterochromatin structured?
Not in use during transcription so tightly coiled and folded so transcription enzymes can’t access it
What are Master Gene Regulators?
Type of Transcription Factors
Give an example of household genes
Metabolic enzymes
How do the genes expressed differ within an organism?
Different cell type within the same organsims have the same genes
Describe the structure of euchromatin when in use
Mainly active and in use so is in an unfolded, open conformation
Why is methylation of globin genes developmentally regulated?
Globin genes are expressed in the RBC lineage only
their promoters are therefore methylated in other cell types