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Genetics and genomes > W4LECT - Epigenetics > Flashcards

W4LECT - Epigenetics Flashcards

1
Q

What is epigenesis?

A

differentiation of cells from a totipotent state in embryonic development

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2
Q

How do different adult stem cells know their fate?

A
  • Myoblasts can only form muscle cells
  • Hematopoetic cells only become blood cells
    => But all have identical DNA sequences.
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3
Q

What is the reason of heterochormia?

A

An Individual Eye with Two Colors

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4
Q

How can just paternal or maternal traits be expressed in offspring?

A

This is called genetic imprinting

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5
Q

How can females express only one X chromosome per cell?

A

X inactivation

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6
Q

How can acquired traits be passed on to offspring?

A

Some changes in gene expression that are, in fact, heritable!

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7
Q

What is Epigenetics?

A

Changes in gene expression without altering the DNA sequence.

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8
Q

What is the difference between GENETICS AND EPIGENETICS?

A
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9
Q

Fill in the squares

A
  1. DNA
  2. DNA-methylation; Histone modification
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10
Q

Fill in the squares

A
  1. Genetic code
  2. Epigenetic code
  3. Epigenome
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11
Q

What are the 4 DNA Molecular Mechanisms that Mediate Epigenetic Phenomena?

A
  1. Transcriptional
  2. DNA methylation
  3. Histone modifications
  4. Chromatin remodelling
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12
Q

DNA methylation
1. Describe DNA methylation

A
  • Methylation of cytosin base
  • Methylation with DNA Methyl-Transferase (DNMT) - General methyl donor (S-adenosyl methionine (SAM) - Change the binding ability of transcription factors
  • Cytosine methylation maintains inactive-condensed chromatin state
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13
Q

DNA methylation
2. Where does DNA methylation take place?

A

It takes place in CpG Islands !

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14
Q

DNA methylation
3. Describe CpG islands

A
  • Large number of CpG dinucleotide repeats
  • Formal definition of CpG is a region with at least 200 bp, a GC percentage greater than 60% (av. 4-6%)
  • p=phosphate
  • 70% of promoters
    contains CpG island
  • Promoters for functional noncoding RNAs such
    as microRNAs
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15
Q

What is the role of DNMT1?

A

Maintenance methylation

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16
Q

What is happening here?

A

2nd round of replication:
-> passive demethylation

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17
Q

What is happening here?

A

Denovo methylation
-> DNMT3A; DNMT3B

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18
Q

What happen if there is deficiency in DNMT1, DNMT3A, DNMT3B?

A

DNMT1 - Embryonic lethal
DNMT3A: Perinatal death
DNMT3B: Embryonic lethal

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19
Q

What are the 5 Effects and consequences of DNA methylation?

A
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20
Q

Modification of Histones
1. Describe Modification of Histones?

A

These modifications alter the binding capacity of the transcription factors to the DNA through:
- Direct effect (charge distribution)
- Altering the secondary, - tertiary structure of the DNA
- Direct effect (charge distribution)
- Altering the secondary, - tertiary structure of the DNA

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21
Q

Modification of Histones
2. What are the 6 main histone modifications?

A
  1. Acetylation /Deacetylation – of Lys (=K)
  2. Methylation – of Lys and Arg (= R)
  3. Phosphorylation – of Ser(S)
  4. Ubiquitination – Lys
  5. Biotinilation- Lys
  6. Citrulination/Deiminálás - Arg
    (H3- tumorigenezis)
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22
Q

Modification of Histones
3. Describe the enzymes that participate in Deacetylation/Acetylation of Histones?

A
  1. HDAC: Histone deacetylase deacetylation
    -> positive charge
    -> histone affinity to the DNA increases
  2. HAT: Histone acetyltransferase
    - Acetylation neutralizes the charge on lysines
    -> histone affinity to the DNA decreases
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23
Q

What is the histone code?

A

Different combinations of histone modifications, may be VERY SPECIFIC to the transcriptional state of the gene.

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24
Q

What are the 3 parts of histone code?

A
  1. Erasers
  2. Writers
  3. Readers
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25
Q

Name the erasers of histone code?

A
  1. Demethylases
  2. Deacetylases
  3. phosphatases
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26
Q

Name the writers of histone code?

A
  1. Methyltransferase
  2. Acetyltransferases
  3. Kinase and ubiquitin ligase
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27
Q

Name the readers of histone code?

A

Bromo, chromo and Tudor domains

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28
Q

What is histone code hypothesis?

A

Different combinations of histone modifications, especially located near or within a gene’s promoter, may be VERY SPECIFIC to the transcriptional state of that gene.

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29
Q

Describe chromatin remodeling?

A
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30
Q

Fill in red squares

A
  1. „Gene silencing”
  2. „ Gene activation” - Transcription
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31
Q

How DNA methylation and histone modification interact and regulates the remodelling?

A
  1. Histone H3-K9 methylation induces DNA methylation: repressed euchromatin + heterochromatin
  2. DNA methylation induces Histone de-acetylation: repressed euchromatin + heterochromatin
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32
Q

Model of gene silencing
1. Fill in the squares

A
  1. Methyl binding proteins bind to DNA
  2. Recruiting deacetylase enzyme
  3. Clearing acetyl groups from Lys
  4. Firm connection between DNA and histones
33
Q

Model of gene silencing
2. Fill in the squares

A
  1. Methylation of H3 Lys9
  2. Recruiting heterochromatine binding proteins
  3. Compact chromatine structure
34
Q

What is the role of DNA methylation and histone modifications ?

A

DNA methylation and histone modifications help to compartmentalize the genome into domains of different transcriptional potential

35
Q

Describe DNA methylation and histone modifications in Euchromatin?

A
  • High histone acetylation
  • Low DNA methylation
  • H3-K4 methylation
36
Q

Describe DNA methylation and histone modifications in Heterochromatin?

A
  • Low histone acetylation
  • Dense DNA methylation
  • H3-K9 methylation
37
Q

What is epigenetic code?

A

Histone-code + DNA-methylation

38
Q

What are the fields that Cytosin methylation is essential?

A
  1. Gene expression
  2. Chromosomal stability
  3. Cell differentiation
  4. Imprinting
  5. X inactivation
  6. Carcinogenesis
  7. Aging
39
Q

Describe DNA Methylation During Human Embryogenesis

A
  1. DNA methylation is largely lost after fertilization, mostly from the paternal genome
  2. Demethylation of the maternal genome continues until the blastocyst stage
  3. DNA becomes remethylated upon differentiation
40
Q

What are Epigenetic changes in identical twins?

A
  1. Comparative monozygotic twins for methylated DNA
  2. Yellow = similar pattern
  3. Red = hypomethylated region in 1 twin compared to other
  4. Green = hypermethylated region in 1 twin compared to other
41
Q

What are Epigenetic changes during aging?

A
  1. different histone variants
  2. altered DNA methylation
  3. altered histone modification
    => genomic instability, including DNA mutations
42
Q

Comparison of the genome methylation in young and elderly

A
43
Q

Explain aging in terms of epigenetic changes

A
  • Measuring human ageing using epigenetic signals
  • ## Developed a model that predicted a person’s age from a saliva sample, the methylation state of about 353 cytosines.
44
Q

What are the Factors may extend life spam?

A
  1. STACs
  2. Metformin
  3. STACs
45
Q

Factors may extend life spam
-> Identify

A
  1. Metformin
  2. STACs
  3. Calorie restriction
46
Q

Factors may extend life spam
-> Identify

A
  1. Rapamycin
  2. Spermidine
  3. Acetyl CoA depletion
47
Q

Describe Anti aging therapy

A
  • It is widely prescribed antihyperglycemic agent
  • Growing evidence for anti aging and anti cancer effect by the induced chromatin remodelling
  • The main problem of therapies inducing epigenetic changes: lack of specificity and tissue- dependent target
48
Q

Describe differences between histone modifications in mortal cells and that in cancer cells

A
  1. Hypermethylation of CpG islands in the promoters of tumor suppressor genes are methylated
    =>Tumor suppressor genes are inactivated
  2. General Hypomethylation (e.g. Line) => Genome instability
49
Q

What are RNA Molecular Mechanisms that Mediate Epigenetic Phenomena

A
  • Post Transcriptional
  • Non coding RNAs
    +) miRNA
    +) siRNA
    +) lncRNA
50
Q

What are the Types of non-coding RNAs?

A
  1. Long ncRNA
    > 200 b
  2. Short ncRNA
    < 200 b
    - siRNA
    - miRNA
51
Q

‘Central dogma’ and aspects of non- coding RNAs functions
-> Identify

A
  1. Chromatin modifications
  2. Poll activity regulation
  3. Transcriptional interference
52
Q

What is the acting mechanism of Long-non cooding RNS?

A
  1. Epigenetic controll
  2. cardiomyocyte differentiation
  3. Inhibition of the odontoblast differentation in dental pulp
53
Q

What is the role of miRNAs?

A
  • Regulate gene expression via post- transcriptional repression;
  • Evoking messenger RNA (mRNA) degradation or translational repression
54
Q

What are the Molecular Mechanisms that Mediate Epigenetic Phenomena in case of protein

A
  • Post Translational
  • DNA remodelling
    (histone modification)
55
Q

X-inactivation (Lyonization) in mammalian females
-> Identify

A

Barr-body

56
Q

Describe Dosage compensation

A

X chromosome inactivation in females (randome)

57
Q

Describe XIST
(X-inactive specific transcript)

A
  1. 17 kb spliced, non-coding RNA
  2. Stable expression only from inactive X
  3. ”Paints” inactive X chromosome
  4. Required to initiate silencing
58
Q

Describe Mammalian X-chromosome inactivation

A
  1. X-chromosome inactivation begins with the synthesis of XIST (X-inactivation specific transcript) RNA from the XIC (X-inactivation center) locus.
  2. The association of XIST RNA with the X chromosome is correlated with the condensation of the chromosome.
59
Q

What are the 3 types of X chromosome inactivation and their consequences?

A
  1. Random XCI
    => Both normal and mutant product made
  2. Skewed XCI ’fortunate’
    => Makes mostly normal product
  3. Skewed XCI ’unfortunate’
    => Makes mostly mutant product
60
Q

Describe Hypohydrotic ectodermal dysplasia

A
61
Q

Describe Skewed inactivation

A
  1. Skewed inactivation modifies the expressivity of X-linked inheritance
    - e.g. Hypohydrotic ectodermal dysplasia
  2. Areas without sweat glands are shown in green in heterozygotes.
62
Q

What is Genomic imprinting?

A

the non-equivalent expression of genes based on parent-of-origin

63
Q

NUCLEAR TRANSPLANTATION DEMONSTRATES THE NON-EQUIVALENCE OF PARENTAL GENOMES
=> What are the consequences of these things?

A
64
Q

What are the difference between maternal imprinting and paternal imprinting?

A
  1. Maternal imprinting
    - limits use of maternal resources by baby in utero
    - „Growth” genes silenced in maternal chromosome
  2. Paternal imprinting
    - maximizes use of maternal resources by baby in utero
    - „Growth inhibitory” genes silenced in paternal chromosome
65
Q

Give 2 examples of disease related to genomic imprinting

A
  1. Angelmann syndrome (AS)
  2. Prader-Willi syndrome (PS)
66
Q

Give 2 examples of disease related to genomic imprinting

A
  1. Angelmann syndrome (AS)
  2. Prader-Willi syndrome (PS)
67
Q

What are the symptoms and imprinted genes suspected or known to be affected of Angelmann Syndrome?

A
  1. Symptoms:
    - Severe motor and mental retardation
    - Paroxysms of laughter
    - Autistic-like behavior
  2. imprinted genes suspected or known to be affected:
    UBE3A: Ubiquitin ligase regulates the release of glutamate receptors in the synapse
  3. expressed gene copy: maternal
68
Q

What are the symptoms, expressed gene copy and imprinted genes suspected or known to be affected of Prader-Willi Syndrome?

A
  1. Symtomps:
    - Moderate mental retardation
    - Severe obesity
    - short stature
    - Poor muscle tone
  2. Numerous imprinted genes in chromosome 15
  3. expressed gene copy: paternal
69
Q

What are the characteristics of Human Epigenome Project (HEP)?

A
  1. Epigenomics Road Map (2008-Present)
    ― Goal: Create map of epigenome in multiple tissue types and cancers
  2. The human genome is the musical score of human existence, but the human epigenome is the conductor.
70
Q

Describe Epigenetics in dentristry

A
71
Q

What is Epigenetics?

A

Epigenetics is the study of heritable mechanisms that affect the transcriptional state of a gene, and generally lead to
monoallelic expression of that gene.

72
Q

Summary of epigenetics
-> Patterns of (1)____ in adult cells (2)____, chromatin structure and gene activation.

A
  1. DNA methylation
  2. parallels cell fate
73
Q

Summary of epigenetics
-> Most ____ and re-established during embryogenesis.

A

DNA methylation is removed at fertilization

74
Q

Summary of epigenetics
- (1)____ keep their (2)_____ giving rise to parental patterns of expression.

A
  1. Imprinted genes
  2. parental pattern of methylation
75
Q

Summary of epigenetics
- Patterns of ___ parallel DNA methylation.

A

histone modifications

76
Q

Summary of epigenetics
- (1)____ and distinctive histone
modifications ((2)____).

A
  1. Active gene regions have little DNA methylation
  2. acetyl groups and H3K4methyl
77
Q

Summary of epigenetics
- X chromosome inactivation in females is correlated with ___ on one chromosome, condensation, inactivation and Barr body formation.

A

extensive CG island methylation

78
Q

Summary of epigenetics
- Alterations in gene and ___ patterns are seen in aging and in cancer.

A

CpG island methylation

79
Q

___ is unmethylated in 93% of inflamed pulp tissue samples

A

Interferon gamma gene

Genetics and genomes (19 decks)

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