Gene Regulation Flashcards
genomic equivalence
each somatic cell type in the body contains the same genome
differential gene expression
each somatic cell has same genome but express a different subset of genes that is regulated at many stages
common control point for gene expression for both bacteria and eukaryotes?
transcription
activators
specific transcription factors that increase gene expression
repressors
specific transcription factors that decrease gene expression/silence genes
How is controlling gene expression in eukaryotes?
since it is complex, there are many additional control points to regulate gene expression
What plays a direct role in regulating transcription?
Histone Modification
What charge are histones?
Positive
What are histones?
Positive charges protein that DNA is wrapped around
Nucleosome
DNA and histone together
Amino end of DNA
N terminus
What does the N terminus of each histone have?
Provides outward forming “histone tails”
How are histone tails modified?
By the addition or removal of specific chemical groups like acetyl groups
What charge is DNA?
negative because of phosphate groups
Histone acetylation
Acetyl groups are attached to a positive charged amino acid in the tails
Positive charges are neutralized so that the tails no longer bind to negative charge phosphates of DNA in neighboring nucleosomes
What does histone acetylation allow?
Promotes a more relaxed structure that allows transcription to occur
Deacetylation
Removal of acetyl groups which promotes compact structure that stops transcription
DNA methylation
Enzymes add methyl groups to certain genes in a DNA molecule and usually turn off the molecule
Example of DNA methylation
Barr Body forms when methyl groups attach to one of a females X chromosome
DNA methylation in genomic imprinting
Deletion in chromosome 15
Father - Pradeep-Will
Mother - Angelman
Methyl groups permanently inactivate the expression of either maternal or paternal genes at the start of development
Epigenetic inheritance
Above the genome- when traits are transmitted by offspring by mechanisms not involved with the nucleotide/DNA sequence
Histone modifications and DNA methylation
What do epigenetic variation explain regarding twins?
One identical twin acquires a genetically based disease while the other does not despite identical genomes
Enhancer
Distant/distal control elements that serve as binding sites for specific transcription factors proteins called activators or repressors
What does the enhancer control?
Controls the initiation of transcription
Where is an enhancer located?
Thousands of nucleotides upstream or downstream from the gene they regulate
What happens when an activator binds to a distal controlled enhancer on a DNA molecule?
Causes a DNA bending protein to bring the bound activators closer to the promoter region on DNA
What happens when activators are near a promoter region?
Mediator proteins help hold the activators close so that general transcription factor proteins and RNA polymerase can come in to make a mRNA and thus activate transcription
Knowing which proteins to make come from?
What protein activators are available in the cell which starts on embryonic development
Scientists used to think that all chromatin during interphase was?
Amorphous - “bowl of spaghetti” forming a tangled mass
What are scientists now discovering about chromatin?
It cloudiest a specific area within the nucleus and has a defined architecture and does not become entangled and some chromatin is highly condensed during interphase
Heterochromatin
Highly condensed chromatin
Traditional loose form of chromatin
Euchromatin
Where is heterochromatin mostly located?
At the centromeres and telomeres and sometimes arms
Which type of chromatin is available for gene expression?
Euchromatin - is accessible for being transcribed
Heterochromatin- is not accessible for being transcribed
Alternative RNA splicing
When different mRNA molecules are produced from the same DNA template depending upon which RNA segments are treated as exons and which are treated as introns
Intron and exons choices are controlled by?
Proteins specific to a cell type affecting where spliceosome makes its cuts in a mRNA molecule
Alternative splicing explains what?
According to Beadle and Tatums hypothesis, “one gene one protein”
We should have 100,000 genes as we have 100,000 proteins
But we have 21,000 genes instead
Are euchromatin and heterochromatin on the same chromosome?
Yes
Diff between liver cell, and lens cell expression?
If albumin gene is expressed, albumin is made (a blood and egg white protein)
If crystalline gene is expressed, only crystalline is made (a protein of the kens of the eye)
Even tho both cells have both genes
bacterial mRNA is typically degraded by enzymes within how long of its synthesis?
few minutes
what does the quick degradation of bacterial mRNA allow for?
the bacteria to change protein production quickly if the environment changes
how long does eukaryotic mRNA last?
typically survives for hours, days, or even months
*mRNA for making hemoglobin are stable and last for months
how many mRNAs do we have?
100,000 mRNA
what have a lifespan before degradation occurs?
completed protein like cyclin proteins at the 3 chemical checkpoints in the cell cycle are relatively short lived to allow the cell cycle to function properly
what happens to mark a protein for destruction?
the cell attaches a small protein called ubiquitin
what happens once ubiquitin is attached?
giant protein/enzyme complexes called proteasomes recognize the ubiquitin tagged proteins that both unfold and begins to degrade them
what happens after proteasomes?
proteases, enzymes that break down proteins, break the proteins down to amino acids
what are linked to mutations of proteasomes?
cancers rendering cell specific proteins impervious to degradation
steps of protein degradation
ubiquitin attaches to protein
complex enters proteasome and turns into peptides
proteases turn peptides into aa
are proteasomes and ubiquitin recycled?
yes
how much of our DNA codes for mRNA that creates proteins?
1.5% (~90 M)
what are RNA that dont code referred to as?
ncRNA (non coding RNA)
examples of ncRNA
every RNA except mRNA
how many ncRNA code for other RNAs>
a small fraction - rRNA, tRNA
what do ncRNAs hint at?
a large and diverse population of RNA molecules in the cell that play critical roles in gene expression
Endogenous way to control translation example
miRNA
what are miRNA?
microRNA are single stranded RNA molecules that either degrade target mRNAs or block target mRNAs, stopping translation
what are miRNAs made from?
a big folded RNA molecule comprised of double stranded hairpin structures
Endogenous
start inside our cells
pre miRNA
double stranded RNA with hairpin turns present in our cells
what enzyme cuts off the hairpin turn?
dicer
what does dicer do?
cuts off hairpin and trims the end and cuts the hairpin turn into small pieces
what happens to one strand of the dsRNA when it is turned into miRNA?
one strand of the double strand is degraded
what happens once miRNA is created?
it links together with an enzyme-protein complex called RISC (RNA induced silencing complex)
what does the miRNA and RISC complex do?
binds to a complementary target on mRNA to either degrade the mRNA or block translation
how much of our genes are regulated by miRNA?
about 1/2
how does the miRNA and RISC complex cut up mRNA?
slicer in RISC cuts it up
Exogenous way to control translation
using siRNAs by the process of RNAi
how did researched discover RNAi?
they were trying to make a purple petunia darker, and added another copy of the gene that makes purple and produced an white petunia instead
what is RNAi?
RNA interference - a process
when an introduced gene is added to existing DNA, the cell thinks the added gene is from a virus, and as the introduced gene is oftentimes slightly different, the cell co-suppresses the expression of all genes (existing and introduced) that express the protein as a precaution
where else has co-suppression been observed?
by injecting cells with dsRNA with the same or similar sequence to the cell’s existing RNA
what RNA do most viruses have?
dsRNA
what does dicer do in RNAi?
interferes by cleaving the dsRNA into small interfering RNA (siRNA) which are 19-25 base pairs long
what do the siRNA doe next after forming?
bind to RISC which binds complementary to mRNA, and slicer stops translation by cutting and turns off gene expression
how is the therapeutic potential to use RNAi process to silence undesirable genes advantageous?
method of choice to defend against viral diseases
alternative to vaccination
may be the cure to turning off genes in many protein diseases
exogenous
starts outside of cell
-virus or researcher injects dsRNA
what can random spontaneous mutations lead to?
cancer
what are the random spontaneous mutations be triggered by?
environmental influences
what is another way of getting cancer?
genetics
oncogenes
cancer causing genes
onco
tumor
proto oncogenes
normal versions of the genes that code for proteins that stimulate normal growth and division
genetic changes that create oncogenes often involve?
increasing the amount of protein product created
cancer cells frequently contain what type of chromosomes?
chromosomes that have broken and rejoined incorrectly from one chromosome to another - translocated fragments
proto
before
healthy cells contain what genes that create proteins necessary in cells for cell division?
tumor suppressor genes
what do tumor suppressor genes do? (3)
inhibit excessive cell division
repair damaged DNA
control cell anchorage
a mutation in a tumor suppressor gene can lead to what?
onset of cancer or uncontrolled cell growth
two key tumor suppressor genes
Ras proto-oncogene
p53 tumor
mutations in ras account for how much of cancer?
30%
mutations in p53 account for how much of cancer?
more than 50%
what does the ras gene code for?
encodes a Ras G protein involved in ultimately stimulating the cell cycle
when does the pathway begin in a cell cycle?
when growth factors bind to receptor tyrosine kinase proteins (monomers) which then form a phosphorylated dimer
what happens once the dimer is made?
activates G protein called Ras, GDP turns to GTP, and this signal passes to a series of protein kinases which activates transcription in the end to stimulate the cell cycle
what is the mutation in ras gene?
turns on Ras G protein even though no growth factor is present, leading to excessive cell division
3 steps involved in cellular response?
reception
transduction
cellular response
what does the transcription factor (activator) do in the ras gene pathway?
turns on a specific gene that increases cell division
what does the p53 code for?
a transcription factor protein that is involved with cell cycle inhibiting proteins (repressor)
what happens if p53’s DNA gets damaged?
the p53 gene does not make the proteins that inhibit the cell cycle and can lead to the development of cancer
how is p53 involved in DNA repair?
it activated a “suicide” gene when DNA is irreparable
nickname of p53
Guardian Angel of the Genome
3 things p53 does to mutated DNA
stop cell division
fix DNA
cause apoptosis for the irreparable ones
how many somatic mutations are needed to produce a full fledged cancer cell?
more than one
relation between life and cancer
longer we live, the more susceptible we are to cancer
how does one get colorectal cancer?
multistep path that starts out with a tumor gradually becoming malignant and invading other tissues (metastasis)
what is the development of colorectal cancer parallel to?
gradual accumulation of mutations that convert proto-oncogenes to oncogenes and knock out tumor suppressor genes
an individual inheriting an oncogene or a mutant allele of a tumor suppressor gene is more likely to?
develop certain cancers
inherited predisposition with breast cancer precentage
5-10% of patients
how common is breast cancer in the US?
2nd most common
mutations in what genes are associated with susceptibility to breast cancer
BRCA 1
BRCA 2
BRCA
BReast CAncer
BRCA 1
60% probability of developing breast cancer before the age 50
BRCA 2
mutations are found in at least 1/2 of inherited breast cancers
wild types of BRCA1 and BRCA2
tumor suppressor genes that regulate how breast cell divide and repair DNA mutations - almost like p53
mutant alleles of BRCA 1 and BRCA2 are recessive or dominant?
recessive
what percentage of human cancers do viruses play a role in?
~15% of the cases
what is the Epstein Barr virus associated with?
mononucleosis
Burkitt’s lymphonma
what type of virus is HPV?
papillomavirus
what is HPV?
most common sexually transmitted infection in the US
what is HPV asoociated with?
cervical cancer
