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Epigenetics Flashcards

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1
Q

Epigenetics

A

Heritable changes in gene function that occur without a change in the DNA sequence

Can be inherited but not DNA changes; can change with different environment

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2
Q

3 modifications of the genome

A

1) DNA methylation
2) histones modification
3) non-coding RNA

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3
Q

DNA methylation: lack of methylation means….

A

Transcription is active

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4
Q

DNA methylation: if methylated….

A

Transcription OFF

Reader recognizes methyl group, enhance blocking of the gene

CpG islands thought out genome, most are methylated

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5
Q

Epigenetics phenomena are characterized by chemical modifications to __ or ___

A

DNA or histones

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6
Q

DNA methylation typically occurs at ____

A

Cytosine bases of DNA, within CpG dinucleotides

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7
Q

CpG islands are associated with

A

5’ regulatory regions of almost al housekeeping genes and 1/2 of almost all housekeeping genes

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8
Q

What happens when promoter CpG islands are methylated

A

Associated genes tend to be transcriptionally inactive

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9
Q

_____ process for maternal demethylation

______ for paternal demethylation

A

Passive for maternal

Active for paternal

As form zygote, everything will be demethylated
Father is actively demethylated in 1-2 division cycles; mother is passively demeythylated until blastocyst (dilution)

*blastocyst –> embryo, maintaining CpG methylation

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10
Q

DNA methylation during mammalian development

A

Wave of demethylation during cleavage, genome-wide methylation after implantation

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11
Q

Extent of methylation in genome of gastrulating embryo is high owing to _____

A

De novo methylation
*tends to decrease in specific tissues during differentiation

*de novo methylation rarely occurs after gastrulation; seen frequently in cancer though

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12
Q

What does dMTase activity do?

A

Demethylase

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13
Q

What does DNA methyl transferase do?

A

De novo methylation

  • need to maintain methylation pattern of cells
  • as replication proceeds, DNAP does not add methyl group on daughter strand; gotta do DNMT maintenance
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14
Q

Transcription factor binding to methylated DNA sequences ____regulates transcriptional output

A

Negatively

TF binds to methylated –> no transcription

DNA sequence regulates TF binding (genetic and fixed)
DNA methylation regulates TF binding (Epigenetic and dynamic)

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15
Q

2 roles of DNA methylation in mammals

A

1) regulation of gene expression
- tissue specific transcription, twin studies, MeCP2: Rett Syndrome

2) Genomic Imprinting

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16
Q

DNA methylation and gene expression twin studies

A

Twins can have Epigenetic tags in different places as they age;

Ex: 50 yr olds have more different Epigenetic tags; rheumatoid arthritis and breast cancer more affected by Epigenetic changes (due to environmental influence) more so than other stuff

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17
Q

Rett Syndrome

A

Autism spectrum disorder with mono genie origin
-progressive neurological developmental disorder
-one of the most common causes of mental retardation in females (1 in 15k females)
-X linked dominant
-period of apparent normalcy: 6-18mos
Life expectancy= 40 years

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18
Q

Mutation in Rett Syndrome

A

MECP2 (CpG binding protein)

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19
Q

MECP2 binds to….

A

Methylated DNA & represses transcription from methylated gene promoters

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20
Q

MECP2 is most abundantly expressed in the

A

Brain

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21
Q

Loss of function of MECP2 in differentiated post-mitotic neurons results in innapropriate_____

Study These Flashcards
A

Over expression of genes with potentially damaging effects during central nervous system maturation

22
Q

Imprinted genes are expressed how?

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A

Preferentially or completely from only one allele (paternal or maternal) depending on the specific imprinted gene under consideration

23
Q

Genomic imprinting is the

Study These Flashcards
A

Unequal expression of the maternal and paternal alleles of a gene

24
Q

Do Epigenetic tags on imprinted genes stay put for life of organism? Exception?

Study These Flashcards
A

YES; but they are reset during egg and sperm formation

If came from mother, will remain maternal; same with dad

25
What happens to imprints in sperm?
Erased and rewritten with the paternal pattern, even with the genes that came from mom
26
What happens to imprints in eggs?
Erased and rewritten with the maternal imprint, even the genes that came from dad
27
If the allele inherited from the father is imprinted it is thereby ___ and only the allele from the ____ is expressed
If the allele inherited from the father is imprinted is is thereby silenced and only the allele from the mother is expressed
28
Which 3 vital roles to imprinted genes play?
1) embryonic growth 2) neonatal behavior 3) tissue or developmental stage specific monoallelic expression patterns
29
Prader-Willi Syndrome
- disorder of genomic imprinting - mental retardation - hyperplasia - paternal deletion of SNRPN; maternal allele of SNRPN is imprinted by methylation (inactivated) - no SNRPN protein at all
30
Angelman Syndrome
- disorder of genomic imprinting - excessive laughter - seizures - mental retardation - maternal deletion (angelman, mothers are angels) (SNRPN, UBE3A) - -
31
Histones can be ___modified in their ____ which protrude from nucleosomes core particle
Histones can be REVERSIBLY modified in their amino terminal tails
32
How can histones be REVERSIBLY modifieD?
Acetylation of lysine; opens zipper, allows for transcription Phosphorylation of serine Methylation of lysine and arginine residues (prevents transcription) Sumoylation
33
What happens when histones methylated and who does this?
``` Closed chromatin Heterochromatin Inactive transcription Writers: methyltransferases Erasers: Histones deacetylases (HDACs) ```
34
What happens when Histones acetylated? Who does this?
Compact chromatin Euchromatin Active transcription Writers: Histones acetyltransferases (HATs) Erases: Demethylase *acetylation increase transcription form (euchromatin) and inactivate transcription thru methylation
35
N termini of core Histones proteins have many lysine residue that have a very ____ charge; these bind tight with negative DNA Tight binding with DNA and Histones associated with
Gene inactivity
36
Positive lysine charge is neutralized by _____ and interaction with DNA is weakened --> transcription can occur
Acetylation
37
Non-COding RNA
NcRNA is a functional RNA molecule that is transcribed from DNA but not translated into proteins MiRNA, siRNA, piRNa, IncRNA
38
Long ncRNAs function in
Chromatin remodeling Transcriptional regulation Post-transcriptional regulation Precursors for siRNAs Ex: X chromosome inactivation (XCI) -2 lncRNAs (Xist and antisense Tsix, negative regulator of Xist)
39
Xist is a ____ transcribed from Xic of inactive C chromosome
LncRNA
40
Xist RNA does what
Covers the entire chromosome and. Silences gene expression through Epigenetic modification of Histones and DNA Xic of inactive X transcribes lncRNA XIst-->covers the entire chromosome and silences gene expression via Epigenetic modification of Histones and DNA
41
What represses Xist and how?
Tsix Both Xist and Tsix produce ncRNA transcripts; Tsix RNA transcript is antisense to Xist Tsix can bind to the Xist sequence and inhibit its action, preventing X-inactivation Depends on who produces what? When 2 X"s coming together, exchanging factors which determines who's making more of what ( hypothesis)
42
How is XIC (X-inactivation center) established?
Pre-XIC: both chromosomes have low conc of Xist Establishment of XIC: one X will make a lot of Tsix ---> there will be reduction of Xist in the area around this X chromosome Therefore, X inactivation is inhibited, and this chromosome will be the active X chromosome
43
Phenotypic plasticity
Ability of one genotype to produce more than one phenotype when exposed to different environments (As the modification of developmental events by environment, or as the ability of an individual organism to alter its phenotype in response to change in environmental conditions
44
What can cause phenotypic plasticity
Environmental effects (ex: hunger winter) may involve Epigenetic changes in gene function that get passed down Adult neuronal plasticity and neurogenic is; changes in chromatin marks & transcriptional networks associated with sustained neuronal activity, mood disorders, addiction
45
Not methylated agouti gene
Continuously active, producing mRNA across lifespan Mouse with yellow fur Develops obesity and diabetes during adulthood
46
Methylated agouti gene
Agouti mRNA made briefly during development Agouti gene silenced remainder of mouse life Healthy mouse, brown fur
47
Are fat yellow mice and skinny brown mice genetically identical
Yes Methylation or lack of determines weight and whether prone to disease or not
48
What happened when fat yellow mouse (agouti gene unmethylated and active) had diet supplement during pregnancy and nursing with additional methyl groups?
Offspring mostly brown and healthy; agouti gene methylated and silenced No dietary supplementation? Offspring yellow and unhealthy
49
Bisulfide conversion of DNA
- method to study changes in epigenome - bisulfide converts C to U if C is NOT METHYLATED - use reverse transcriptase, PCR, DNA sequencing, or methylation specific restriction enzyme digestion to determine methylation status of specific strand Methylated cytokines don't react with bisulfide; allows us to determine methylation status of different genes
50
How to detect DNA methylation with methylation sensitive restriction enzymes?
Methylation insensitive (MspI) cuts enzyme; methylation sensitive (HpaIIdoes NOT cut DNA where it is methylated !!! (Both restriction enzymes cut same sequence aka isoschizomer) Methylation insensitive is insensitive and CUTS

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