2.19 Epigenetics Flashcards
Set of all the RNAs (both coding and noncoding) produced by a cell or a population of cells
Transcriptome
Set of all the proteins produced by the cell at a particular point in time under certain environmental conditions
Proteome
True or false
Less nurtured rats had multiple epigenetic marks that silenced these genes
True
True or false
Nurtured rats handled stress better because nothing was restricting or silencing the activity of these genes
True
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
Rearranging misplaced tags/markers
Epigenetic therapy
Control of gene expression
DNA methylation
Histone tail modification
Different types of RNAs
Angelman Syndrome: __ gene deletion
Maternal
Prader-Willi Syndrome: ___ gene deletion
Paternal
True or false
Epigenetics can have transgenerational effects
True
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
Some environmental exposure in one generation having effects on future generation
Transgenerational effect
True or false
Epigenetic changes accumulate over time
True
Older twins have more (red/yellow) in their DNA than the younger twins
Red
Happens when two active X chromosomes interact but the other is silenced
X inactivation
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
Inactive X chromosome shows DNA methylation of ___
CpG islands
Inactivated X chromosome packaged as heterochromatin
Barr bodies
XX females have __ Barr body/ies
1
XXX females have __ Barr body/ies
2
Dispersed, beads on a string, with active histone tail molecules that tag DNA
Active chromosomes (Euchromatin)
These are open and accessible to transcription factors and other proteins
Genes are turned ON
Active chromosomes
Euchromatin
Tightly bound and condensed, with inactive histone tail modifications
Inactive chromosome (Heterochromatin)
Structural proteins that zip the DNA up
DNA is methylated
Less accessible for transcription and therefore silenced
Genes are turned OFF
Heterochromatin
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 __
11
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
