differentiation Flashcards
(17 cards)
how do changes in the gene expression underlie the diversity of cell types in the body
-all cells have the same gene content but different sets of proteins
-cell diversity primarily results from differences in gene expression
-the final state of the cell is called the terminally differentiated state -> cells can still go through mitosis despite being fully differentiated
-cells change the expression profile in response to signals and other cues in the environment
-cells express a fraction of their genes -> e.g. neural cells would be repressed in bones
-cells often express different genes in disease state
what is the stepwise restriction in potency
-totipotent - can differentiate into any cell
-pluripotent
-multipotent
-bipotent
-unipotent
what does stages of differentiation correlate with
-stepwise expression of different regulatory transcription factors
-researchers use expression of different genes (markers) to track the stages of differentiation
how does the level of transcription affect the level of expression
-if the different cells/ tissue have differences in gene expression we call that differential gene expression
-transcriptome- all genes that are actively being transcribed
-proteome- all proteins being made
what happens when DNA binding proteins bind to the DNA backbone
-they reach into the major groove to form very specific bonds:
=a binding site is a stretch of DNA with a sequence that is recognised and bound by the transcription factor- the bonds are H bonds and are not stable
=other names for binding site - cis acting element- regulatory element - enhancing - silencing
why are regulatory elements usually found in and around a gene
-transcription factors bind in clusters
-enhancer= binding sit for transcriptional activators
-silencers= binding site for transcriptional repressors
-we often use enhancer to refer to both enhancers and silencers - enhancers are promiscuous (will work on any gene)
how do inputs alter gene expression
-inputs often referred to as a genetic switch- each switch is responding to extrinsic or intrinsic regulation
what do regulatory transcription factors modulate
-the level of expression of many genes a single transcription factory can create an expression profile
how can gene activity be regulated by feedback loops
-positive = activate expression of one TF -> activates downstream genes
-negative = activation of gene 3 -> target is repressor, which represses gene 3 expression
what is transcription factor activity dependent on
-extrinsic signals
-intrinsic factors
-regulatory binding sites
what happens with muscle differentiations
- muscle specific proteins -> muscle specific actin -> myosin II (allows contractility) -> tropomyosin -> muscle specific enzyme
whats myoD
-transcription factor
-expressed on in muscle precursors and muscle cells
-controls expression of genes for muscle differentiation
-maintains its own expression
is myoD sufficient for muscle cell differentiation: modifcation experiment
-fibroblasts do not normally express myoD or other muscle specific proteins
-experiment : transfect (introduce a modified gene into cell or an animal) fibroblasts with activated myoD gene
-result: fibroblast now differentiate into muscle
-conclusion: myoD is sufficient to direct muscle cell fate in fibroblast
what are fibroblasts
-connective tissue cells that are real to mesenchymal cells
-commonly used in tissue culture
is myoD required for muscle cell differentiation
-mice lacking the function of myoD to develop with normal skeletal muscle
-conclusion: myoD is not required for muscle cell differentiation
-a second gene myf5 acts redundantly with myoD
-mice lacking both myoD and myf5 function lack al skeletal muscle, so both genes do have an important role in muscle differentiation
-we often describe genes as being necessary/required and/or sufficient
embryonic stem cells vs adult stem cells
-embryo= most muscle comes from somites
-adult= muscle cells are renewed by satellite stem cells that lie muscle fibres
-satellite cells express Pax7 gene -> line muscle fibres in basement membrane- if given the right signals, they willl divide to create a new muscle
why are blood cells another classic model for differentiation
-in mammalian embryo, blood cells are first made in the yolk sac and then the liver- > in adults, blood is made in the bone marrow
-as cells travel toward terminal differentiation, they express different sets of transcription factors
