Regulate transcription and translation 2

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  • Created by: Hindleyc
  • Created on: 12-04-19 18:58
Where the associations of histones with DNA is weak what is the DNA-histone complex
less condensed (loosely packed)
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In this condition what is the DNA
Accessible by TF
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What can these do
initiate production of mRNA, that is, can switch gene on
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Where this association is stronger what is the DNA-histone complex
more condensed (tightly packed)
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in this condition what is the DNA
not accessible by TFs
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What can't these do
initiate production of mRNA, that is, the gene is switched off
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What does condensation of the DNA histone complex do
inhibits transcription
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How can it be brought about
by decreased acetylation of the histones, methylation of DNA
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What is acetylation
process whereby an acetyl group is transferred to a molecule
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What is deacetylation
reverse reaction where an acetyl group is removed from a molecule
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What does it do
increase positive charges on histones and therefore increases their attraction to the phosphate groups of DNA
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As the association between DNA and histones is stronger what is the DNA
not accessible to transcription factors so these TF cannot initiate mRNA production from DNA (in other words gene is switched off)
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What is methylation
Addition of a methyl group (CH3) to a molecule
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In this case where are the methyl groups added to
cytosine bases of DNA
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What does methylation normally do
inhibits transcription of genes in 2 ways
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how
Preventing binding of TF to the DNA (so RNA polymerase can't bind) and attracting proteins that condense the DNA histone complex by inducing deacylation of the histones) making the DNA inaccessible to TF
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To inactivate a gene what happens to histones, DNA, DNA-histone complex, Chromatin type, TF
decrease, increase, more condensed (tightly packed), heterochromatin, no access
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to Activate a gene what happens to histones, DNA, DNA-histone complex, Chromatin type, TF
Inc, dec, less condensed (loosely packed), euchromatin, access
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What did experiments on rats show
Female offspring who received good care when young respond better to stress in later life and themselves nurture their offspring better
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What is thought that in sperm and eggs during the earliest stages of development
specialised cellular mechanism searches the genome and erases its epigenetic tags in order to return the cells to a genetic clean slate
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However what do a few epigenetic tags
escape this process and pass unchanged from parent to offspring
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What are epigenetic changes part of
normal development and health but they can also be responsible for certain diseases
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What does altering any of the epigenetic processes cause
abnormal activation or silencing of genes
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What have such alterations been associated with
a number of diseases including cancer
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in some cases what happens
activation of a normally inactive gene can cause cancer, other cases inactivation of a normally active gene that gives rise to the disease
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in 1983 what did researchers find that diseased tissue taken from partients with colorectal cancer have
less DNA methylation than normal tissue from the same patient
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What does increased DNA methylation normally do
inhibit transcription (switches off gene) meaning that these patients with less DNA methylation would have higher than normal gene activity - more genes were turned on
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What is known that there are specific sections of
DNA (ones near regions called promotor regions) that have no methylation in normal cells
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However in cancer cells what happens to these regions
become highly methylated causing genes that should be active to switch off- abnormality happens early in development of cancer
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What do epigenetic changes do
don't alter seq of bases in DNA but they can increase incidence of mutations
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What do some active genes normally help
repair DNA and so prevent cancers
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In inherited cancers what is it found that inc methylation of these genes has led to
these protective genes being switched off and as a result damaged base sequences in DNA aren't repaired and so can lead to cancer
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So what are many diseases such as cancer triggered by
epigenetic changes that cause certain genes to be activated or silenced
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What is it therefore logical to try
to use epigenetic treatments to counteract these changes
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What do these treatments use
drugs to inhibit certain enzymes involved in either histone acetylation or DNA methylation such as drugs that inhibit enzymes that cause DNA methylation can reactivate genes that have been silenced
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What must epigenetic therapy be
specifically targeted on cancer cells because if drug were to affect normal cells they could activate gene transcirption and make them cancerous so causing the very disorder they were designed to cure
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What is another use of epigenetic in disease treatment
has been the development of diagnostic tests that help to detect the early stages of diseases such as cancer brain disorders and arthritis
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What can these tests identify
level of DNA methylation and histone acetylation at an early stage of disease allowing those with these diseases to seek early treatment and so have a better chance of a cure
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In eukaryotes and some prokaryotes, what can translation of the mRNA produced from target genes be inhibited by
RNA interference (RNAi)
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how inhibited
by breaking mRNA down before its coded information can be translated into a PP
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What is one small RNA molecule that may be involved
small interfering RNA (siRNA)
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how does the mechanism involving small double stranded sections of siRNA operate
An enzyme (dicer enzyme) cuts large double stranded molecules of rNAinto smaller sections called siRNA
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what does one of the 2 siRNA strands combine with
an enzyme
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What does the siRNA molecule do
guides the enzyme to a messenger RNA molecule by pairing up its bases with the complementary ones on a section of the mRNA molecule
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once in position what does the enzyme do
cuts the mRNA into smaller sections
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So what is the mRNA no longer capable of
being translated into a polypeptide
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What does this mean
that the gene has not been expressed that is, it has been blocked
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overall steps
enzyme cuts double stranded RNA broken up into siRNA = siRNA with paired bases then one of the 2 strands of siRNA combines with an enzyme forming siRNA single stranded with unpaired bases then this pairs with complementary base on a mRNA strand
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so
enzyme cuts mRNA into smaller sections
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How is double stranded RNA formed
When synthesised (made by special regulartory gene) self complement - fold back on itself by complementary bp to become double stranded then dicer enzyme splits into siRNA= short section separate and becomes single stranded with specific sequence
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rhen
associate with proteins- risc= RNA inducing silencing complex which broken down into separate strands so can bind to mRNA- other discarded then binds to mRNA by complementary bp'ing silencing gene that contains complementary mRNA -
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what is the mRNA
cut therefore can't make functioning protein
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Any mRNA molecules with base seq complementary to 20 base pairs
the siRNA will bind causing risc to cut the mRNA molecule in 2 and this cleaved mRNA can no longer br used in translation and is broken down by nuclease enzymes
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