Transcription factors Flashcards
Which 3 main TFs maintain ES cell pluripotency?
Oct4, Sox2 and Nanog
What is the evidence supporting Oct4 as an important player in maintaining ES cell pluripotency?
Oct4 knockout turns inner mass cells into trophectoderm
Two key properties of an ES cell?
Self-renewal
Pluripotency
Which are the MASTER TRANSCRIPTION FACTORS (MTFs) for ES cells? (which in particular?)
Oct4 - MAIN
Sox2
Nanog
What is meant by pluripotency?
The ability to differentiate into many cell types
What are: OCT4, SOX2 and NANOG?
Transcription factors with essential roles in early development that are required for the propogation of undifferentiated embryonic stem (ES) cells in culture
How do master transcription factors (MTFs) ensure ES cell pluripotency?
Pluripotency genes (eg STAT3) are ACTIVATED
Lineage specific genes (eg HOXB1) are REPRESSED
What is the MTF for red blood cell and platelet development?
GATA-1 (a ZnF TF)
What does GATA-1 regulate? How?
Erythrocyte cell fate:
- activates and represses genes equally
- collaborates with other TFs, eg KLF1
What is GATA-1’s pre-cursor? Which proteins does it complex with to form:
1) Red blood cells
2) Platelets
GATA-2 (oligopotent precursor (CMP))
1) KLF1
2) Fli-1
What is the most important epigenetic modification?
DNA methylation
Studies on lineage-specific MTFs are fundamental to understanding mechanisms of cell fate determination and lineage plasticity. Why?
Because they are involved in lineage commitment from hematopoietic stem cells through:
1) Regulating the activation of specific gene programs, and
2) Suppressing multipotential and alternate lineage gene programs.
What are the target transcription factor genes of GATA-1?
Itself, GATA-2, KLF-1, etc… There are many
Which three types of genes does GATA-1 target?
1) Transcription Factors
2) Signalling Molecules
3) Cytoskeletal Proteins
Give three features of KLF-1
1) erythroid specific
2) ZnF
3) transcriptional activator
What determines cell fate?
Mutually antagonistic transcription factors
What are the main transcription factors involved in determining whether a haemopoietic stem cell will develop into a platelet or a red blood cell? Which are antagonistic?
Gata2, Gata1, KLF1 and Fli-1
KLF1 promotes platelet formation and inhibits rbc
Fli-1 promotes rbc formation and inhibits platelets
Gata1 inhibits Gata2
Gata 2 PROMOTES Gata1
Give an example of transdifferentiation and how it can be induced.
Can convert heart FIBROBLASTS directly into heart MUSCLE CELLS.
By forcing the expression of an appropriate combination of factors (not Oct4, Sox2, Klf4 and Myc) like Gata4, Mef2c and Tbx5.
What is an iPS cell?
Induced Pluripotent Stem cell
Which 4 main MTFs were identified by Yamanaka in 2006 as important for inducing pluripotent stem (iPS) cells from fibroblasts?
Oct4
Sox2
Klf4
Myc
How efficient is the reprogramming of a fibroblast into an iPS?
VERY LOW… only works for 1/10,000 cells
What is the main obstacle to reprogramming?
Epigenetic modification: DNA methylation cannot be reversed in mammalian cells
What is the principle of Waddington’s epigenetic landscape?
A stem cell ‘rolls down’ a landscape and falls into different valleys. With each valley it falls into, it becomes more specialised, and cannot go back from there. e.g. first trough decides whether it will be neuron/skin cell, or fibroblast/muscle.. etc..
What regulates the transcriptional programme which determines cell fate?
Master transcription factors (e.g. Oct4 for stem cells)
