Epigenetics Flashcards

1
Q

What is Epigenetics involved in

A

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

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2
Q

What is Epigenetics

A

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

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3
Q

Epigenetics

A

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

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4
Q

Two forms of inheritance of epigenetic modifications

A
  1. Somatic – Cell differentaiation + X-Inactivation
    • Heretible through somatic cell division
      Example – bone cells remember that they are bone cells and make other bone celle
  2. Transgeneration – Genetic imprinting
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5
Q

Epigentic modifcations can be…

A

Programs (intensional) – X-inactivation + Somatic + Imprinting

OR

Environmental – smoking + Toxins + Phase of moon + Stress
- Change gene expression = chnage phenotype –> passed down

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6
Q

Euk Genome

A

Euk genome is compacted –> To turn genes on = need to get to DNA

Epigenetics expose or close chromatin structure

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7
Q

Closed vs open gene

A

Closed = Off gene

Open = Expressed

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8
Q

Epigenetics + Condensed genome

A

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

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9
Q

Acylation vs. Methylation

A

Histone tail Acetylation – relaxes chromatin (high expression)

DNA methylation – Leads to tighter compaction (low expression)

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10
Q

Condensed vs. Open Chromatin

A

Condensed chromatin – Transcriptionally inactive

Open Chromatin – Transcriotionally Active

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11
Q

How does Chromatin condense/uncondense (mechanism)

A

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

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12
Q

Possibilities for Histone Tail Modifications

A

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

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13
Q

Histone Stucture

A

4 different tails – 2 of each –> 8 total

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14
Q

lncRNA + Chromatin remodeling

A

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

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15
Q

Different hitsone tail modifications…

A

Recruit different remodeling complexes

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16
Q

Second form of epigenetics

A

DNA methylation

***Cytosine can be methylated

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17
Q

CpG sites

A

5’ Cytosine - Phosphate - Guanine 3’

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18
Q

Affect of CpG sites

A

CpG sites = target for methylation

***Methylation tends to happen when have a C next to a G

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19
Q
A

Answer: 2, 7, 3, 8 – 5’ C –> G 3’

***If have one on top then have one on bottom

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20
Q
A

Notice non-uniform distribution of CpG –> CpG cluster near beginning of gene near promoter

Vs. GpC are scattered

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21
Q

Clusters of CpG

A

CpG islands – cluster if CpG sequences

***CpG islands are frequently located in promoter regions

22
Q

Distrubution of CpG throughout the genome

A

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

23
Q

How does DNA methylation inhibit transcription

A
  1. Through Inhibition
  2. Through Recuritment
24
Q

DNA methylation Inhibition

A

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

25
Q

DNA methylation Through Recuritment

A

DNA methylation can recurit proteins that condense chromatin OR can recurit repressors that block transcription

26
Q

Affect of DNA methylation

A

DNA methylation at CpG islands tend to inhibit transcription

27
Q

DNA mtheylation of CpG islands (Overall)

A

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

28
Q
A

Answer: Writter –> Add signal to genome

29
Q
A

Answer: Earser

30
Q
A

Answer: Activator AND Reader

Activator –> Bind = promotes gene expression

31
Q

Are all histone modifications heretible?

A

Not all histone modifications or DNA methylations are heritable BUT some are

***The ones that are = epigenetic (Epigenetic MUST be heritable)

32
Q

Inheritance of DNA methylation

A

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

33
Q

Inheritance of Histone Modifications

A

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

34
Q

X-Inactivation + Epigenetics

A

X-inactivation is an epigenetic process – daughter cells remember which X-chromosme is condensed into a Barr Body

35
Q

X-Inactivation Skewing

A

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)

36
Q

X-Inactivation process

A

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

37
Q

Stem cells + epigenetics

A

Differentiation of stem cells into specific cell types requires epigenetic modifications

38
Q

Affect of reserach on stem cells

A

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

39
Q

Stem cell cycke

A

Toptipotente embryonic stem cells –> Pluripotentent embryonic stem cells –> Multipoetent (Adult) stem cell –> Unipotent Stem cell

40
Q

Types of Stem cells

A
  1. Ectoderm
  2. Mesoderm
  3. Endoderm
41
Q

What does each type of stem cell become

A

***Each become certain things (Endo vs. ecto = different tissues)

Ectoderm –> Lung + Pancerus

Mesoderm –> Heart + Muscle + Red Blood Cells

Endoderm –> Skin + Nueron

42
Q

Embyonic stem cells

A

Embryonic stem cells = totipotent = can turn into any cells)

43
Q

Adding epigenetic modifcations to stem cells

A

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

44
Q

What happens once stem cells are differentiated

A

Once differentiated = All they can do is make more of the same cell type

45
Q
A

Answer: Start with Endoderm

46
Q

Where are Totipotent And pluripotenet stem cells

A

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

47
Q

Whare are Multipotent stem cells found

A

Multipotent stem cells can be found in small numbers in some tissues in adults or children

48
Q

How do you get stem cells

A

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

49
Q

Reducing Reliance on Fetal Tissue

A

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

50
Q

Reprogramming adult stem cells

A

Works for some adult stem cells

51
Q

Questions in Stem cells

A
  1. How is epigenetic remodeling Accomplished
  2. What is the efficacy of this remodeling
  3. Are there new epigenetic modifications created