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Epigenetics represents a form of inheritance that is superimposed on the genetic inheritance based on DNA.
Covalent modifications on core histone tails |
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Epigenetic inheritance is based on |
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Other molecules and is less permanent than a change in the DNA sequence. |
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1.Histone modification 2.DNA methylation: CpG and genomic imprinting 3.X chromosome inactivation |
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The covalent modifications of histones in nucleosomes serve as |
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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” |
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Modification of histones occur |
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Definition
on the 8 N-terminal “histone tails”
Acetylation and Methylation on Lysine |
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Covalent modifications on core histone tails:
Acetylation and Methylation on Lysine |
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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 |
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What does Phosphorylation of serine add to the histone |
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Adds a negative charge to a histone. |
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Methylations,acetylations and phosphorylations are reversible with what enzyme. |
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Enzymes: - Histone acetyltransferase (HAT) - Histone deacetylase complex (HDAC) - Histone methyltransferase - Histone demethylase |
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The acetylation of lysines on the n-terminal tails tends to |
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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. |
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Schematic diagram showing how the histone code could be read by a code-reader complex |
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DNA repair Gene expression
Particular combinations of marks on chromatin can attract additional protein complexes that execute appropriate biological functions at the right time. |
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Some specific meanings of the histone code |
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M: methylation, A: acetylation, P: phosphorylation AA code: K: Lysine; S: Serine |
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Spreading of chromatin condensation |
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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 |
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Condensed chromatin (heterochromatin): |
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Definition
no gene activity Not easily accessible for the transcription machinery. |
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Not condensed chromatin(euchromatin): |
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Chromosomes: hetero- and euchromatin |
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Definition
Centromeres are embedded in a stretch of special centric heterochromatin, CENP-A, a variant form of histone H3 |
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Definition
Of a region of chromatin to a fixed site can form a barrier that stops the spread of heterochromatin. |
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Definition
of barrier proteins to a group of nucleosomes can prevent heterochromatin spreading. |
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Definition
erase the histone marks that are required for heterochromatin to spread. |
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Centromere during mitosis |
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Definition
Centromeres are embedded in a stretch of special centric heterochromatin CENP-A, a variant form of histone H3. |
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Organization of the chromatin that forms the centromere |
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Definition
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Centric and pericentric heterochromatin |
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Direct inheritance of centromeric heterochromatin |
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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. |
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Model of direct inheritance of centromeric heterochromatin |
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Definition
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The packaging of DNA in chromatin can be inherited during chromosome replication |
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Definition
Specialized chromatin components are distributed to each daughter chromosome after DNA duplication |
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Term
cell memory stored as chromatin- based epigenetic information in the genes of eucaryotes |
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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. |
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Schematic illustration of cell memory stored as chromatin-based epigenetic information in the genes of eucaryotes |
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Definition
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Gene activator proteinspromote transcription initiation by changing the chromatin structure of the regulatory sequences and promoters of the gene |
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Definition
-Nucleosome remodeling -Nucleosome removal -Nucleosome replacement -Covalent histone modifications |
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Alteration in chromatin structure can stimulate transcription |
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Definition
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Eucaryotic activator proteins direct alterations in chromatin structure to stimulate transcription |
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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. |
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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) |
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The alterations can persist for variable length of time |
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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. |
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Transcriptional activation |
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Definition
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Term
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several activator proteins work together producing a transcription rate that is much higher than the sum of the activators alone. |
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Transcriptional repression |
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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 |
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Alteration in chromatin structure can lead to gene repression: |
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Definition
1.Repressor recruits a chromatin remodeling complex 2. Repressor attracts a histone deacetylase 3. Repressor attracts a histone methyl transferase |
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Epigenetics: DNA methylation |
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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. |
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The methylation has no effect on the base pairing. |
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Form of methylation can lead to |
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Modifies CpG nucleotides (CpG islands). The maintenance DNA methyltransferase is active after replication. |
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dynamic during vertebrate development. |
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Shortly after fertilization |
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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 |
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new patterns of methylation are established, |
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they can be propagated through rounds of DNA replication by the maintenance methyltransferase |
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-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. |
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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. |
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Imprinted genes are somehow protected from |
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Definition
the wave of demethylation that takes place shortly after fertilization. |
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In vertebrates, genomic imprinting is restricted |
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Definition
to placental mammals and many of the imprinted genes are involved in fetal development. |
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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. |
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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. |
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Definition
Females have two X-chromosomes. Males have one X- and one Y-chromosome |
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- 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. |
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Mechanism to equalize the dosage of gene products between males and females: X-chromosome inactivation in female somatic cells. |
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X-chromosome inactivation |
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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 |
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The X-chromosome inactivation is initiated and spreads |
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Definition
from a single site in the middle of the X-chromosome, the X-inactivation center (XIC) |
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Definition
X Inactivation Specific Transcript |
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The XIST RNA is not translated into |
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Definition
protein and remains in the nucleus, where it eventually coats the entire inactive X-chromosome. |
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correlates with spread of gene silencing. |
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XIST RNA is an unusual RNA molecule, which is expressed from |
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the inactive X-chromosome and needed for the inactivation |
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the X-chromosome heterochromatin is characterized |
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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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