Epigenetic Phenomena Flashcards
What epigenetic change happens at CpG islands?
methylation of cytosines
Where are CpG islands often found?
close to 5’ end
How do CpG islands relate to the expression pattern of neighboring genes?
CpG methlyation can shut down expression of neighboring genes
Hypomethylation can reactivate what sort of elements?
transposable elements
What enzymes introduce de novo DNA methylation?
DNMT 3a and 3b
What enzyme maintains DNA methylation?
DNMT1
What is the function of methylcytosine binding proteins?
shutdown txn by binding to metyhlated cytosines
What proteins can MBPs directly associate with?
HDACs
At what terminus do modifications of histone proteins occur?
N-terminus
Methylated histones bind to what protein?
HP1
HP1 proteins can bind what?
histone methylases
What are chromatin barriers also known as? What is their function?
where cytosine methylation stops
to inhibit gene activity
What is the function of imprinting?
to mark whether a chromosome has come from the mother or the father
When does imprinting take place?
gametogenesis
What is the function of XIST?
to inactivate the X-chromosome
What is uniparental disomy?
when an individual only has maternally or paternally imprinted homologues
What disease is an example of uniparental disomy?
Beckwith-Wiedemann Syndrome
What chromosome is affected in Beckwith Wiedeman syndrome?
both homologues of chromosome 11 are inherited from the father
What receptor is overexpressed in BWS?
insulin-like growth factor 2
Prader Willi Syndrome results from what?
deletion on parental chromosome 15
What disease results from a deletion on maternal chromosome 15?
Angleman
Antibodies against what are produced during systemic lupus erythematosus? What cells are belived to be involved?
nuclear components
T cells
The activity of what protein is reduced during SLE in T cells?
DNMT1
HDAC inhibitors are used during what disease?
chronic lymphocytic leukemia
DNMT inhibitors are used in what disease?
acute myeloid leukemia
Name a DNMT inhibitor
5-azacytidine
Where is epigenetic information stored?
methylation pattern of cytosine and covalent modification of histones
What do writers do?
methylate cytosine
What do copiers do?
copy methylation pattern from an old strand to a new strand of DNA
What action do readers perform?
recognize methylated DNA and initiate silencing of affected chromosome regions
What section of DNA is composed of methylated cytosines? What does this do?
CpG dinucleotide repeats
silences that gene
What three types of genes are often silenced by CpG dinucleotide repeats?
highly repetitive DNA, telomeres, centromeres
Where are CpG island often found? Are they methylated?
5’ UTR of genes
no
What will hypomethylation often do to transposable elements?
reactivate them
How is de novo methylation introduced into an unmethylated strand of DNA?
DNMT 3a and 3b
What enzyme is responsible for maintaining the pattern of methylation in DNA?
DNMT1
Which strand, parent or daughter, is methylated?
parent
What protein binds methylated cytosines? What is the function of this protein?
methylcytosine binding proteins (MBPs)
to repress txn
What is the function of H2Az?
increase txn of adjacent genes
What proteins do methylated histones bind to?
HP1
What happens to histones after they become de-acetylated?
they are often methylated
What is the function of HP1 proteins?
HP1 binds to methylated histones
What is the function of a boundary element?
to impede the spread of histone methylation
What are boundary elements also known as?
chromatin barriers
What are the functions of boundary elements?
separating active and inactive chromosomal regions
What two biological processes are influenced by imprinting?
Development and maturation of gametes
How does imprinting affect development?
cell-type differentiation
What does imprinting do to DNA?
silences it
When does imprinting take place?
gametogenesis
Is the parent of origin re-written? When?
yes
during gametogenesis
How does the XIST relate to imprinting?
XIST designates which x-chromosome is to be inactivated
What happens to the XIST on the x-chromosome to be inactivated?
it is transcribed
What is uniparental disomy?
when an individual only has maternally or paternally inherited homologues of a chromosome
Beckwith-Wiedemann Syndrome arises from what type of chromosomal aberration?
uniparental disomy
How does Beckwith-Wiedemann Syndrome arise?
inherit two paternal homologues of chromosome 11
Beckwith-Wiedemann Syndrome features an abundance of what receptor?
insulin-like growth factor 2
Prader-Willi and Anglemann syndrome both feature what kind of aberration on what chromosome?
deletions on chromosome 15
If the deletion is on maternal chromosome 15, what disease arises?
Anglemann
If the deletion is on paternal chromosome 15, what disease arises?
Prader-Willi
During systemic lupus erythematosus, antibodies against what are created?
nuclear components
What type of immune cells are involved in SLE?
T-cells
HDAC inhibitors have proven useful in what diseases?
chronic lymphocytic leukemia
What does 5-azacytidine inhibit?
DNMT1
Inhibition of DNMT causes what to the genome?
hypomethylation
5-azacytidine has been approved in the treatment of what disease?
acute myeloid leukemia
What is the role of imprinting?
to mark a chromosome as either paternal or maternal in origin
When does imprinting take place?
gametogenesis
What two syndromes are caused by deletions on chromosome 15?
Anglemann and Prader-willi
Deletion of paternal 15 = ?
Prader willi
Deletion of maternal 15 = ?
Anglemann
HDAC inhibitors are effective against?
chronic lymphocytic leukemia
Name a DNMT inhibitor
5-azacytidine
What does 5-azacytidine do?
cause hypomethylation of the genome
What has 5-azacytidine been approved for the use of?
acute myeloid leukemia
What is the XIST gene?
X-chromosome inactivating specific transcript
Where is XIST located?
X-chromosome inactivating center (XIC)
What causes Lupus?
epigenetic changes in T cells
Regarding T-cell genome, what do SLE patients show?
global hypomethylation
Treating patients with what kind of drugs causes SLE-like symptoms?
DNMT inhibitors (5-azacytidine)
