Epigenetics Flashcards
What is Epigenetics involved in
Part of stem cells (Bine cells rembering they are bone cells and making more bone cells)
Part of X-Inactivation –> form of epigenetic modifications
Things that grand parents do affect us
What is Epigenetics
We don’t turn on all of the genes at the same time –> epigenetic allows cells to remember which genes to turn on or off
Epigenetics
Heritable changes in gene expression that do not change the DNA sequence
- Still modify genome in way that influence how genes are expressed
***Epigenetic = a special kind of gene regulatory system
Two forms of inheritance of epigenetic modifications
- Somatic – Cell differentaiation + X-Inactivation
- Heretible through somatic cell division
Example – bone cells remember that they are bone cells and make other bone celle
- Heretible through somatic cell division
- Transgeneration – Genetic imprinting
Epigentic modifcations can be…
Programs (intensional) – X-inactivation + Somatic + Imprinting
OR
Environmental – smoking + Toxins + Phase of moon + Stress
- Change gene expression = chnage phenotype –> passed down
Euk Genome
Euk genome is compacted –> To turn genes on = need to get to DNA
Epigenetics expose or close chromatin structure
Closed vs open gene
Closed = Off gene
Open = Expressed
Epigenetics + Condensed genome
Epigenetic modifications alter the accessibility of genes (and their promoters) by altering chromatin structure
Chromatin Remodeling and gene accessibility is regulated through epigenetic modifications
- Includes Histone modifications + ncRNA + DNA methylations
Acylation vs. Methylation
Histone tail Acetylation – relaxes chromatin (high expression)
DNA methylation – Leads to tighter compaction (low expression)
Condensed vs. Open Chromatin
Condensed chromatin – Transcriptionally inactive
Open Chromatin – Transcriotionally Active
How does Chromatin condense/uncondense (mechanism)
Histone = Positiveley Charged
DNA = Negitiveley charged
Histone = clamps in and holds onto DNA –> BUT acytelation of histone tails decreases the positive charge = The histone can’t hold DNA as tightly = opens DNA
Possibilities for Histone Tail Modifications
There are Lots of possibilities – Different Amino Acids on Histone tails can be:
1. Phosphorylated
2. Acylated
3. Methylated
4. Ubiquitnated
Histone tails can be modified in different ways – Different combinations change regions of chromatin
Histone Stucture
4 different tails – 2 of each –> 8 total
lncRNA + Chromatin remodeling
lncRNA can influence chromatin remodeliing
Some lncRNAs recruit remodeling complexes that can condense or decondense chromatin
Regulating expression of lnRNA = influence chromatin structure –> certain lncRNA affect in difefrent ways
Different hitsone tail modifications…
Recruit different remodeling complexes
Second form of epigenetics
DNA methylation
***Cytosine can be methylated
CpG sites
5’ Cytosine - Phosphate - Guanine 3’
Affect of CpG sites
CpG sites = target for methylation
***Methylation tends to happen when have a C next to a G
Answer: 2, 7, 3, 8 – 5’ C –> G 3’
***If have one on top then have one on bottom
Notice non-uniform distribution of CpG –> CpG cluster near beginning of gene near promoter
Vs. GpC are scattered
Clusters of CpG
CpG islands – cluster if CpG sequences
***CpG islands are frequently located in promoter regions
Distrubution of CpG throughout the genome
CpG are scattered throughout the genome BUT before a gene have cluster of CpG sites = have CpG islands near promoter
If have a CpG island = know gene is nearby and that the gene is regulated by epigenetics
How does DNA methylation inhibit transcription
- Through Inhibition
- Through Recuritment
DNA methylation Inhibition
Methylation can prevent activators + transcription factors + RNA polymerase from binding to DNA
Example – Activator binds to enhancer promoting transcription –> if have methyl = activator can’t bind = prevent transcription
DNA methylation Through Recuritment
DNA methylation can recurit proteins that condense chromatin OR can recurit repressors that block transcription
Affect of DNA methylation
DNA methylation at CpG islands tend to inhibit transcription
DNA mtheylation of CpG islands (Overall)
Not all promoters have CpG islands = not all genes are regulated through epigenetics
Not all CpG sites are methylated
No one CpG site controls gene expression –> Don’t need to methylate specific site or specific number of sites
Answer: Writter –> Add signal to genome
Answer: Earser
Answer: Activator AND Reader
Activator –> Bind = promotes gene expression
Are all histone modifications heretible?
Not all histone modifications or DNA methylations are heritable BUT some are
***The ones that are = epigenetic (Epigenetic MUST be heritable)
Inheritance of DNA methylation
Methylated DNA acts as a template for methyl transferases –> After DNA replication in interphase – methylated DNA on the old strand can recuruit DNA methylases that dd methyl groups to the new strand
After replication – 1/2 of the stands (the old strands ) are methylated BUT have readers that go in to methylate the other strand to you end with fully methylated DNA
Inheritance of Histone Modifications
Still researching BUT it is thought that the patterns on the original chromatin structure are “read” then “written” onto new chromatin complexes
Inherit by looking at histone modifications –> give information to writter –> Will give same patern in same reader
X-Inactivation + Epigenetics
X-inactivation is an epigenetic process – daughter cells remember which X-chromosme is condensed into a Barr Body
X-Inactivation Skewing
Some cells express Mom X
Some cells express Dad X
***Can lead to different patterns + can lead to different degrees of X-linked disease presentation (2 twins but only one has an X-linked disease –> X-inactivation in tissue)
X-Inactivation process
Have X-inactivation center – Codes for 2 noncoding RNAs
1. X-ist (Short)
2. TSix (reverse of Xist – Long)
Have Pairing AT Xic and recruit proteins –> Centers will break apart (depair) and all of the protein will go to one X-chromsome (leaves one empty)
- Which X-chromsome Proteins will go to is random
The chromsome with the proteins will promote transcription of Long RNA and the other Chromosome with non protein will transcribe the short ncRNA
One with no proteins + transcribing the short RNA = will recruit other proteins = Spread = condensed
Stem cells + epigenetics
Differentiation of stem cells into specific cell types requires epigenetic modifications
Affect of reserach on stem cells
Research on stem cells could:
1. Increase understanding of disease
2. Generate healthy cells to replace damaged cells (“regernarative medicine”)
3. Test new Drugs for saftey + efficacey
Stem cell cycke
Toptipotente embryonic stem cells –> Pluripotentent embryonic stem cells –> Multipoetent (Adult) stem cell –> Unipotent Stem cell
Types of Stem cells
- Ectoderm
- Mesoderm
- Endoderm
What does each type of stem cell become
***Each become certain things (Endo vs. ecto = different tissues)
Ectoderm –> Lung + Pancerus
Mesoderm –> Heart + Muscle + Red Blood Cells
Endoderm –> Skin + Nueron
Embyonic stem cells
Embryonic stem cells = totipotent = can turn into any cells)
Adding epigenetic modifcations to stem cells
Add epigenetic modifications Between Toptipoente –> Pluripotent stem cells (After 1 week of embryo stage)
Adding epigenetic modifcations = start to tramscribe genes –> Become Endo or Ecto or Mesoderm stem cells
What happens once stem cells are differentiated
Once differentiated = All they can do is make more of the same cell type
Answer: Start with Endoderm
Where are Totipotent And pluripotenet stem cells
Toptipotent and PLuripotent embryonic stem cells are found in fetla tissue
Embryonic stem cells can be replicated in lab conditions without inducing differentiation – replicate stem cells indefinitely
Whare are Multipotent stem cells found
Multipotent stem cells can be found in small numbers in some tissues in adults or children
How do you get stem cells
Big challenege –> Big challenge in reserach in stem cell therapy
Challenge = where to get stem cells from
There is a lot of controvery over using fetal tissue
Reducing Reliance on Fetal Tissue
To reduce reliance on fetal Tissue:
1. Ongoing efforts to reprogram adult stem cells to pluripotent stem cells
2. Perinatal stem cells found in amniotic fluid off a potential new source of stem cells for research
Reprogramming adult stem cells
Works for some adult stem cells
Questions in Stem cells
- How is epigenetic remodeling Accomplished
- What is the efficacy of this remodeling
- Are there new epigenetic modifications created
