Genetics Quiz 2: Epigenetics and DNA methylation
there are over 20-_____ genes in human genome and over _____ distinct cell types. thus
20-25,000 genes over 200 distinct cell types THUS each cell must select some genes to turn on or silence.
A beta cleavage followed by gamma cleavage generates
A-beta peptide fragments
what is the viable yellow agouti allele
A^vy
what is mouse color from
Agouti gene
DNA methylation at promoters of BACE1 and PSEN1 is low in
Alzheimer's neurons basically in normal cells, there's more methylation at the promoters in the CpG island in BACE1 and PSEN1 and so the gene gets silenced.
Alzheimers disease is characterized by inappropriate cleavage of
Amyloid precursor protein (APP) cleaved wrong leading to beta-amyloid plaques
Beta cleavage is facilitated by
BACE1
many CpG sites next to each other can be called a
CpG island
in DNA methylation, cytosine can be methylated at
CpG sites
what methylates CpG sites
DMNT
expression of A^vy can be modulated by
DNA methylation
the phenotype of mice directly reflects the amount of
DNA methylation at the pseudo-exon
what is DNA and histones like in euchromatin
DNA unmethylated histones acetylated
main thing used in treatments for these disorders
HDAC inhibitors
Gamma cleavage is facilitated by
PSEN1
even tho the Avy gene comes in to make the a allele come out more and cover up the A agouti, what can turn it the other way
The Avy comes with a CpG island!!! This means it can be methylated and deactivated this leads to a "pseudoagouti" which is almost agouti but not quite because the yellow got silenced again
how does agouti transcription work in hair follicles
begins at an alternative TSS in Exon 2 produces the appropriate amount of gene product basically exon 2 controls the gene expression
Gene transcription can be regulated thru interaction of
cis-acting elements (promoters, enhancer and silencer sequences) and DNA binding proteins like transcription factors
epigenetic modifications can integrate developmental events and environmental cues as well as contribute to
disease progression
examples of abnormal epigenetic landscapes
diseases like cancer and neurodegenerative diseases
what does A^vy do
ectotopic (inappropriate) expression of the "a" gene. overexpresses the a allele, makes it yellow even if A is present.
how are methylation patterns inherited
epigenetic imprinting
what is it called when u modify histones, chromatin state, or DNA
epigenetic regulation because it shows heritable effects without changing DNA sequence itself
A allele causes
eumelanin (dark pigment) Agouti usually dominant
when is the level of methylation established
fetal development by the nutritional state of the mother
when the CpG island on the promoter is unmethylated then what
gene can be transcribed NO METHYL = CAN BE TRANSCRIBED
all cells have the same ____ but different _____
genome epigenomes
healthy mom =
healthy babies
highly methylated health and diet
healthy weight supplemented diet (folate, b12, etc.)
DNA methylation stimulates
heterochromatin
epigenetics
how diff cell types use the same genome
inheritance of traits not coded for in the DNA sequence can be referred to as
imprinting
where are CpG sites normally
in or near promoter regions and participate in gene silencing
what is A^vy from
insertion of a pseudo exon before the actual exon 2.
after DMNT starts methylating,
methyl binding proteins (MBD) recognize the modification and recruit HDACs to begin deacetylating nearby histones
besides cis acting elements what else can provide more regulation
modifying histones, chromatin state, and chemical alterations to DNA
unmethylated health and nutritition
obesity control diet aka ectotopic expression
a allele causes
phaeomelanin (yellow)
methylated Avy phenotype
pseudoagouti Avy is there but it got deactivated by the methylation
as development happens, cells become differentiated and programs of gene expression become more and more
restricted
methylation at CpG islands in or near promoters can
silence gene expression
When a promoter is methylated (with the CpG in it) what happens to the gene
silenced
what does the HDAC trigge r
stimulates heterochromatin around CpG islands
methylation at the pseudo-exon can
suppress phenotypes and improve health
what makes it hard for transcription factors to find their binding sites
the methyl groups protrude into the major groove of the helix making it hard for transcription factors to find their sites
Avy mothers frequently pass on this allele along with the same methylation state to
their pups Avy yellow (unmethylated) make Avy yellow (unmethylated babies)
what happens when these fragments come together
they make harmful amyloid plaques
what is special about CpG
this is where methylation can happen can silence genes
unmethylated phenotype Avy
yellow Avy doing its work without any interference. Masks the agouti
