Epigenetics Study of biological mechanisms that will switch genes on and off. Chemical modifications can turn genes on and off Diet, environment, exercise, sleep, relationships/interactions, aging, etc. can cause the chemical modifications
Gene Regulation What is a gene? All cells have ‘the same’ genome Why not make a big toe in your liver? Remember that ‘ball of cells’ called a blastocyst?
Morula – about 4 days after fertilization Your first BIG decision If you’re a cell in this ball, what are you?
No turning back – Trophoblast may become ICM ICM CAN’T become t-blast
Development Cells in the morula can become ANYTHING Trophoblast develops into placenta ICM develops in to YOU Cells in the ICM are ‘pluripotent’ They can become ‘any’ of your cells Nerve cells, hemopoietic cells, muscle, etc They ARE stem cells
No turning back – Trophoblast may become ICM ICM CAN’T become t-blast But all the DNA is the same
Gene Regulation Obj 9, what do you have?
Gene Regulation Transcription factors, activators are proteins Promotors and enhancers are (usually) regions RNA polymerase transcribes the gene Binds to promoter region and transcription factors Repressors and silencers slow transcription down or turn genes off.
Gene Regulation IF transcription factors and activators are PROTEINS, then… They are coded for by genes! So genes control gene expression!!!
Gene Regulation In trophoblast, transcription factor Cdx2 is made (gene turned on) Cdx2 helps turn on other transcription factors for placental development It also DOWN REGULATES Oct4 and Nanog Oct4 and Nanog are transcription factors for the ICM => turn on genes for YOU Oct4 and Nanog also DOWN REGULATE Cdx4
Gene Regulation And the story of you begins
Late Blastocyst Ectoderm – brain and spinal cord Mesoderm – muscle, bones, heart, kidney Endoderm – internal organs
Late Blastocyst “Derm” layers are a ‘one way’ street. Can’t go back – stem cells with MUCH less plasticity
Development It’s pretty complex, but… Oct4 and Nanog transcription factors start a cascade “Growth Factor” proteins (morphogens)are turned on They, in turn, regulate other genes
Development Growth factors include: BMP (bone Morphogenic Protein), Fgf and retinoic acid BMP was first discovered as bone-growth regulator But ALSO in embryonic development and adult tissue homeostasis A common theme – one gene controlling MANY different things EPIGENETICS!!!!!
Development Fgf and retinoic acid gradient lay down Anterior-Posterior patterning This in turn, turns on/off HOX genes 13 HOX genes repeated on 4 different chromosomes (gene duplication)
Development HOX genes lay down the body pattern This causes genes to turn on and off
Development How do you turn genes off ‘permanently’? Methylation of DNA This causes genes to turn on and off
Histone modification can turn genes off – make them inaccessible
Development How do you turn genes off ‘permanently’? Methylation of DNA This causes genes to turn on and off Evidence suggests fetal alcohol syndrome may be from methylation Turns off genes too early => reduced development
Development Back to HOX genes HOX genes lay down the body pattern This causes genes to turn on and off
Development More RA leads to different Hox gene regulation => more vertebrae
So... How do you make a snake? Either turn off the signal that designates legs or fail to ‘hear/respond’ Repeat the ‘backbone’ location over and over and over... in pythons, fore limbs ‘lost’ b/c of first, hind limbs b/c of latter
Development Turn on transcription factor genes to turn on genes for those areas In the case of limb formation…
AER – Apical Ectodermal Ridge Limb bud development Thickened ridge of ectodermal cells
Development When the AER is replaced by Fgf (Fibroblast Growth Factor), limb grows normally STRONGLY suggests AER secretes Fgf => (Apical Ectodermal Ridge-Derived Fibroblast Growth Factor)
Tbx 5 – fore limb development Tbx 4 – hind limb When Fgf is applied to flank between to limb buds NEW limb shows characteristics of both
Development It has A LOT to do with when a gene is turned on, for how long, and how ‘loud’
Look Ma!!! Segments!
Your Questions?
Homework Tomorrow – work on project in class For Wed – Obj 5 (?), 6 Test Friday Project reports after break
Other Telomeres and exercise