2.19 Epigenetics Flashcards by Karla Guntayon

Set of all the RNAs (both coding and noncoding) produced by a cell or a population of cells

Transcriptome

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Set of all the proteins produced by the cell at a particular point in time under certain environmental conditions

Proteome

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True or false

Less nurtured rats had multiple epigenetic marks that silenced these genes

True

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True or false

Nurtured rats handled stress better because nothing was restricting or silencing the activity of these genes

True

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Study of changes in gene expression that are stable over rounds of cell division, and sometimes between generations, but do not involve change in the underlying DNA sequence of the organism

Epigenetics

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Rearranging misplaced tags/markers

Epigenetic therapy

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Control of gene expression

DNA methylation
Histone tail modification
Different types of RNAs

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Angelman Syndrome: __ gene deletion

Maternal

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Prader-Willi Syndrome: ___ gene deletion

Paternal

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True or false

Epigenetics can have transgenerational effects

True

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Analyzing patterns of famine and other information in the village archives, it was found that the effects of famine are still evident in the people almost a century later despite not having experienced famine themselves

Overkalix study

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Some environmental exposure in one generation having effects on future generation

Transgenerational effect

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True or false

Epigenetic changes accumulate over time

True

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Older twins have more (red/yellow) in their DNA than the younger twins

Red

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Happens when two active X chromosomes interact but the other is silenced

X inactivation

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Allows males and females to have the same dose of genes on the X chromosome even though females have to X’s and males have only one

X inactivation

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Inactive X chromosome shows DNA methylation of ___

CpG islands

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Inactivated X chromosome packaged as heterochromatin

Barr bodies

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XX females have __ Barr body/ies

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XXX females have __ Barr body/ies

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Dispersed, beads on a string, with active histone tail molecules that tag DNA

Active chromosomes (Euchromatin)

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These are open and accessible to transcription factors and other proteins
Genes are turned ON

Active chromosomes

Euchromatin

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Tightly bound and condensed, with inactive histone tail modifications

Inactive chromosome (Heterochromatin)

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Structural proteins that zip the DNA up
DNA is methylated
Less accessible for transcription and therefore silenced
Genes are turned OFF

Heterochromatin

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The inactive X chromosome in a female somatic cell, rendered inactive in a process called __

Lyonization

States that in cells with multiple X chromosomes, all but one is inactivated during mammalian embryogenesis.

Lyon Hypothesis

Mechanisms for epigenetic control

DNA methylation Histone Modification Other regulatory mRNAs

Methylated DNA = gene (silencing/expression)

Silencing

Unmethylated DNA = gene (silencing/expression)

Expression

Used to maintain genomic stability

DNA methylation

Intergenic regions and repetitive elements are usually methylated because these are correlated with jumping genes called __

Transposons

DNA methylation usually occurs at ___ turning it into ___

Cytosine; | 5-methylcytosine (mC/5mC)

A sequence often near promoters of genes where methylation usually occurs

CpG Islands

True or false | CpG islands are usually methylated

False | They are protected from methylation to allow for expression

CpG islands are usually site for methylation due to it being ___

Symmetrical

Can maintain the methylation state after replication by using the hemimethylated DNA as a substrate, and then methylating the other strand accordingly

DNMT1

Proteins that bind CpG islands are called ___

Methylated CpG binding proteins or MeCPs

Have a transcriptional repression domain | Recruit other factors that condense the chromatin

Methylated CpG binding proteins

Mediated by methylation to render gene inactive

Imprinting

Marking genes as paternal or maternal in origin, in other words, parent-specific gene activation

Genomic imprinting

Occurs when there is a deletion in the 15q11-q13 region of the paternal chromosome 15

Prader Willi syndrome

Occurs when there is a deletion in the 15q11-q13 region of the maternal chromosome 15

Angelman syndrome

Gene involved in Angelman syndrome

UBE3A

Gene involved in Prader-Willi syndrome

SNRPN

In Angelman syndrome, UBE3A protein is involved in what pathway

Ubiquitin pathway

In Prader-Willi syndrome, SNRPN gene is involved in what process

mRNA splicing

Obesity Hypogonadism Mild to moderate mental retardation Hyperphagia

Prader-Willi syndrome

``` Microcephaly Ataxic gait (uncoordinated muscle movement) Seizures Inappropriate laughter Severe mental retardation ```

Angelman syndrome

True or false | Methylation of C in CpG islands affects globin genes in human embryonic blood cells

True

True or false | The activity of the globin genes correlates directly with the methylation of their promoters

False | Correlates indirectly: high globin activity, unmethylated promoter

The erythroid-specific LCR for the beta globins is upstream of epsilon on chromosome __

Function as super-enhancers, establishing open chromatin

LCRs

Methods of demethylation

Passive demethylation | Active demethylation

Could happen by dilution when DNMT1 fails to maintain methylation marks after replication and cell division

Passive demethylation

Important for wiping the slate clear during development

Active demethylation

Active demethylation is done by specific enzymes ___

Ten-Eleven Translocation, TET family of enzymes

In an active demetylation, hydroxymethylcytosine is a likely ___ and is ___

intermediate; regulatory

The bisulphite sequencing cannot distinguish __ and __

mC and hmC

Distinguish between mC and hmC by running bisuflphite sequencing twice

Oxidating bisulfite sequencing

Yield information about formylcytosine

Resduced Bisulfite sequencing

Correlated with gene opening and activation

Histone Acetylation

Known to occur on lysine residues in the amino terminal tails of histone molecules

Acetylation

Changes the charge from positive to neutral amide, which decreases the affinity of histone to the DNA

Acetylation (of lysine changes)

Histone methylation occurs in the amines of __ and __, but there is no change in the charge of the amines

Lysine | Arginine

Active locus | Around promoter area

Methylation of histone 3's lysine 4 (H3K4me)

Inactive locus | Spread over the gene in constitutive heterochromatin (stable inactivation, such as centromeres)

Methylation of histone 3's lysine 9 (H3K9me)

Inactive locus | Spread over the gene in facultative heterochromatin

Methylation of histone 3's lysine 27 (H3K27me)

Largely unchanged among different cell types Always condensed and thus essentially inactive Found in the regions near the chromosal centromere and at chromosomal ends (telomeres)

Constitutive heterochromatin

Vary among different cell types and tends to be associated with cell type At times condensed, but at other times it is actively transcribed and thus appears as euchromatin

Facultative heterochromatin

True or false | Histone modification is stable through rounds of cell division

False | Unlike DNA methylation, it does not seem to be as stable

DNA methylation tends to ___; Histone methylation tends to ___

Silence genes; | Activate or inactivate genes

lncRNAs

Long noncoding RNAs

Have greater sequence specificity due to length During trnascription, ther are attached or close to their gene of origin May serve as guide or scaffold for attaching histone modifying enzymes

lncRNAs

Part of machinery that leads to silencing of one of X chromosomes in females 17-kb, spliced polyadenylated

Xist RNA

Expressed from one of the X chromosomes, coats it, and leads to silencing of the other X chromosome

Xist RNA

GAL gene's expression by RNA polymerase II may be suppressed by:

lncRNA transcription on the other side | lncRNA association with hsitones to prevents its modifications to open the DNA

Some sort of immune system (anti-transposon, anti-virus) in mammalians

PIWI-interacting RNAs (piRNAs)

Regulatory RNA which forms a complex with PIWI proteins that can be imported to the nucleus to methylate transposone genes and silence them

piRNAs

True or false | piRNAs can also direct DNA methylation at sites other than transposable elements

True

Proportion of individuals carrying a particular variant of a gene

Penetrance

When not all carriers of a certain dominant allele in a population end up expressing the trait

Incomplete penetrance