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Epigenetics
Mid Term Prep
62
Biology
Graduate
02/22/2015

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Term
Epigenetics
Definition
Epigenetics represents a form of inheritance that is superimposed on the genetic inheritance based on DNA.

Covalent modifications on core histone tails
Term
Epigenetic inheritance is based on
Definition
Other molecules and is less permanent than a change in the DNA sequence.
Term
Epigenetic mechanisms
Definition
1.Histone modification
2.DNA methylation: CpG and genomic imprinting
3.X chromosome inactivation
Term
Chromatin packing
Definition
Term
The covalent modifications of histones in nucleosomes serve as
Definition
A recognition sites for protein modules that can effect gene expression.

A large number of these modifications occur on the 8 N-terminal “histone tails”
Term
Modification of histones occur
Definition
on the 8 N-terminal “histone tails”

Acetylation and Methylation on Lysine
Term
Covalent modifications on core histone tails:

Acetylation and Methylation on Lysine
Definition
- Acetylation of removes the positive charge on lysine.
-Methylation (mono-, di-, or tri-) on lysine keeps the positive charge on lysine.
- Acetylated lysine cannot be methylated, and vice versa
Term
What does Phosphorylation of serine add to the histone
Definition
Adds a negative charge to a histone.
Term
Methylations,acetylations and phosphorylations are reversible with what enzyme.
Definition
Enzymes:
- Histone acetyltransferase (HAT)
- Histone deacetylase complex (HDAC)
- Histone methyltransferase
- Histone demethylase
Term
The acetylation of lysines on the n-terminal tails tends to
Definition
loosen chromatin structure, in part because adding an acetyl group to lysine removes the positive charge
- profound effect of the histone
modification is to attract specific proteins.
Term
Schematic diagram showing how the histone code could be read by
a code-reader complex
Definition
Term
Histone code hypothesis:
Definition
DNA repair
Gene expression

Particular combinations of marks on chromatin can attract additional protein
complexes that execute appropriate biological functions at the right time.
Term
Some specific meanings of the histone code
Definition
M: methylation,
A: acetylation,
P: phosphorylation
AA code: K: Lysine; S: Serine
Term
Spreading of chromatin condensation
Definition
- Gene regulatory protein binds with histone modifying enzyme
-Recognition of signal by code-reader complex
- Chromatin remodeling complex is ATP dependent
- Gene expression is prevented
Term
Condensed chromatin (heterochromatin):
Definition
no gene activity Not easily accessible for the transcription machinery.
Term
Not condensed chromatin(euchromatin):
Definition
gene activity
Term
Chromosomes: hetero- and euchromatin
Definition
Centromeres are embedded in a stretch of special centric heterochromatin, CENP-A, a variant form of histone H3
Term
Tethering
Definition
Of a region of chromatin to a fixed site can form a barrier that stops the
spread of heterochromatin.
Term
Tight binding
Definition
of barrier proteins to a group of
nucleosomes can prevent heterochromatin spreading.
Term
Barrier proteins can
Definition
erase the histone marks that are required for heterochromatin to spread.
Term
Centromere during mitosis
Definition
Centromeres are embedded in a stretch of special centric heterochromatin CENP-A, a variant form of histone H3.
Term
Organization of the chromatin that forms the centromere
Definition
Term
Centric and pericentric heterochromatin
Definition
Term
Telomere
Definition
Term
Direct inheritance of centromeric heterochromatin
Definition
Chromatin structures can be directly inherited.
The H3-H4 tetrameres from each nucleosome on the parental DNA helix are directly inherited by the daughter DNA helices at
the replication fork.
Term
Model of direct inheritance of centromeric heterochromatin
Definition
Term
The packaging of DNA in chromatin can be inherited during chromosome replication
Definition
Specialized chromatin components are
distributed to each daughter chromosome after DNA duplication
Term
cell memory stored as chromatin- based epigenetic information in the genes of eucaryotes
Definition
Genes can be packaged into a large variety of different chromatin structures. Some of these structures have a special effect on gene expression that
can be directly inherited as epigenetic information when a cell divides.
Term
Schematic illustration of cell memory stored as chromatin-based epigenetic information in the genes of eucaryotes
Definition
Term
Gene activator proteinspromote transcription initiation by changing the chromatin structure of the regulatory sequences and promoters of the gene
Definition
-Nucleosome remodeling
-Nucleosome removal
-Nucleosome replacement
-Covalent histone modifications
Term
Alteration in chromatin structure can
stimulate transcription
Definition
Term
Eucaryotic activator proteins direct alterations in chromatin structure to stimulate transcription
Definition
Making the underlying DNA more accessible, thereby facilitating the assembly of general transcription factors
,specialized transcription factors (mediator), and RNA polymerase at the promoter.
Term
Gene activation:
Definition
1.Histone acetyl transferase (HAT): acetylation of lys 9 of H3, and lys 8 of H4.
2.Binding of gene activator
3.Histone kinase: phosphorylation of ser of H3
4.HAT:acetylation of lys 14 H3
5.Binding of general transcription factor TFIID
6. Binding of chromatin remodeling complex
(SWI/SNF)
Term
The alterations can persist for variable length of time
Definition
-Some cases chromatin modifications are rapidly reversed: for a quick on and off switch of gene expression in response to external signals.
- In other cases, altered chromatin structure persist to generate a memory that can extend into the next
cell-generation.
Term
Transcriptional activation
Definition
Term
Transcriptional synergy
Definition
several activator proteins work together producing a transcription rate that is much higher than the sum of the activators alone.
Term
Transcriptional repression
Definition
Many eukaryotic repressor proteins can act through more than one mechanism:
- Repressor: recruits a chromatin remodeling complex
- Repressor acts as histone deacetylase
- Repressor acts as histone methyl
transferase
Term
Alteration in chromatin structure can lead to gene repression:
Definition
1.Repressor recruits a chromatin remodeling complex
2. Repressor attracts a histone deacetylase
3. Repressor attracts a histone methyl transferase
Term
Epigenetics: DNA methylation
Definition
Cytosine can be methylated in“CpG islands”
,located in the 5’region of a
gene.



Similar to the modification of the
histone tails, the pattern of the DNA
methylation can be inherited.
Term
Methylation
Definition
The methylation has no effect on the
base pairing.
Term
Form of methylation can lead to
Definition
Gene repression
Term
DNA methylation
Definition
Term
DNA methyltransferase
Definition
Modifies CpG nucleotides (CpG islands).
The maintenance DNA methyltransferase
is active after replication.
Term
DNA methylation patterns
Definition
dynamic during vertebrate development.
Term
Shortly after fertilization
Definition
There is a genome-wide wave of demethylation, when the vast majority of methyl groups are lost from the DNA.

Later in development, new methylation patterns are established by several de novo DNA methyltransferases
Term
new patterns of methylation are established,
Definition
they can be propagated through rounds of DNA
replication by the maintenance methyltransferase
Term
Gene repression
Definition
-DNA methylation in the promoter region of a gene or in its regulatory sequences can interfere directly with the binding of proteins required for transcription.
- Proteins that bind specifically to methylated DNA can block the access of other proteins.
Term
Genomic Imprinting
Definition
- The expression of a small minority of genes depends on whether they have been inherited from the mother or the father: while the paternally inherited gene copy is active, the maternally inherited gene is silent, or vice-versa.
Term
Imprinted genes are somehow protected from
Definition
the wave of demethylation that takes place shortly after fertilization.
Term
In vertebrates, genomic imprinting is restricted
Definition
to placental mammals and many of the imprinted genes are involved in fetal development.
Term
Mono-allelic expression
Definition
One of the two copies of certain human genes is expressed. The decision which of the alleles is expressed and which is silenced can be random. But once made, it is passed on to progeny cells.
Term
Identical twins
Definition
Their genomes have the same sequence of nucleotides,but when their histone modification and DNA methylation
patterns are compared, many differences are observed.
- These differences are correlated with their age and time they spent apart from each other.
- It is believed that some of these changes are the result of environmental factors.
Term
X-chromosome
Definition
Females have two X-chromosomes.
Males have one X- and one Y-chromosome
Term
X-chromosome
Definition
- Female cells contain twice as many copies of X-chromosome genes than male cells do.
- The X-chromosome is large and contains more than 1000 genes, while the Y-chromosome is small and contains
approximately 100.
Term
Dosage compensation
Definition
Mechanism to equalize the dosage of gene products between males and females: X-chromosome inactivation in female
somatic cells.
Term
X-chromosome inactivation
Definition
One of the two X-chromosomes in each somatic cell becomes highly condensed into a type of heterochromatin (Barr body).
The Barr-body is located near the nuclear membrane. The initial choice which chromosome to inactivate is random. But once inactivated, it remains silent throughout all subsequent cell divisions.
-Every female is a mosaic of clonal groups of cells in which either Xm or
Xp is silenced.
-The inactivation is not always permanent
Term
The X-chromosome inactivation is initiated and spreads
Definition
from a single site in the middle of the X-chromosome, the X-inactivation center (XIC)
Term
XIST
Definition
X Inactivation Specific Transcript
Term
The XIST RNA is not translated into
Definition
protein and remains in the nucleus, where it eventually coats the entire inactive X-chromosome.
Term
The spread of XIST RNA
Definition
correlates with spread of gene silencing.
Term
XIST RNA is an unusual RNA molecule, which is expressed from
Definition
the inactive X-chromosome and needed for the inactivation
Term
the X-chromosome heterochromatin is characterized
Definition
by a specific variant of histone 2A, hypoacetylation of H3 and H4, which
makes most of the X-chromosome unusually resistant to transcription.
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