White: Control of gene expression 1&2 Flashcards

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1
Q

Gene regulation requires

A

Recognition sites for DNA binding proteins-TATA

Gene regulatory proteins-TFs

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2
Q

Recognition sequences can be proximal or distal to first exon: T or F

A

True- they can be either proximal or distal

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3
Q

Transcription factor modules and which of these are required

A

DNA-binding module–required
Activation module–required
Dimerization module– not required
Regulatory module– not required

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4
Q

Helix-turn-helix

A

Simplest most common DNA binding motif
Two alpha-helices
Longer helix= recognition module–DNA binding module fits into its major groove

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5
Q

Zinc finger domain

A

DNA binding motif includes Zn domain
Binds to major groove of DNA
Found in tandem clusters
Stabilizes interaction with DNA, multiple contact points

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6
Q

Leucine zipper motif I

A

Two alpha-helical DNA binding domain
Grabs DNA like clothespin
Activation domain overlaps dimer domain
Interaction b/w hydrophobic AA side chains (leucines)

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7
Q

Leucine Zipper motif II

A

Dimerizes through leucine zipper region
Interactions b/w hydrophobic AA side chains (leucines)
Leucine residue every 7 AAs down one side of a-helix, forms zipper structure

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8
Q

Helix-loop-helix domain

A

Consists of short Alpha-chain connected to longer alpha chain
Can be Homo or Heterodimers
3 modules- DNA binding domain, Dimerization domain, Activation domain

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9
Q

Hereditary spherocytosis and zinc finger domain

A

HS can be caused by mutation in Zinc finger protein gene Klf1
Mutation is Glu to Asp in exon 3
HS KLF1 binds to opposite strand as the wildtype protein, which will NOT allow transcription to start

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10
Q

Identification of transcription factors

A

Describe one way TFs are identified

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11
Q

Gene control region

A

DNA region involved in regulating and initiating transcription of a gene

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12
Q

Gene control region includes

A

Promotor- TFs and RNA poly II assemble here

Regulatory sequences for binding of regulatory proteins which control rate of assembly process at the promoter

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13
Q

Activation of transciption

A

DNA looping and a mediator complex allow the gene regulatory proteins to interact with the proteins at the promoter
The mediator serves as an intermediary between gene regulatory proteins and RNA polymerase II

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14
Q

Transcription factors bind to DNA in _______,

Fact about affinity in this process

A

Nucleosomes
Transcription regulators bind to DNA in nucleosomes with lower affinity than naked DNA because surface of nucleotide recognition sequence may be facing inward when attached to nucleosome

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15
Q

Ways to overcome affinity problem w/nucleosomes

A

Nucleosome remodeling
Nucleosome removal
Histone replacement
Histone acetylation

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16
Q

Gene repressors inhibit transcription in what ways

A

Competitive DNA binding
Masking of the activation surface
Direct interaction with TF- repressor binds DNA and blocks assembly of TFs
Recruitment of chromatin remodeling complexes
Recruitment of histone deacetylases
Recruitment of histone methyl transferase

17
Q

Proteins can be either activating or repressing depending on

A

The composition of complexes at gene regulatory sites

18
Q

7 ways gene regulatory proteins are controlled

A
Synthesis
Ligand binding
Covalent modification-phosphorylation
Addition of subunit
Unmasking
Nuclear entry
Proteolysis
Must be able to describe two of these
19
Q

Negative vs positive control of alternative splicing

A

Negative control- Repressor molecule prevents splicing machinery access to splice site
Positive control- Activator recruits and helps directs splicing machinery

20
Q

Spatial localization of mRNAs

A

mRNA leave nucleus through pores
They travel to destination using cytoskeletal motors
Randomly move and can be trapped by special proteins
Non trapped RNA is degraded

21
Q

Regulation by RNA stability

A

Poly-A tail– once reduced to 25 nucleotides, two pathways converge to degrade mRNA

  • Decapping- mRNA degraded from 5’ end
  • mRNA degraded from 3’ end through poly-A tail
22
Q

IREs IRAs

A

IRE- Iron responsive elements- recognition sites for binding
IRP- Iron responsive regulatory protein- Aconitase
IRP binds IRE

23
Q

Effect when IRP binds IRE at 5’ ferritin mRNA vs binding IRE at 3’ transferrin receptor mRNA

A

Iron starvation
IRP binds IRE at 5’ ferritin mRNA- no ferritin- translation is blocked
IRP binds IRE at 3’ transferrin receptor mRNA- Transferrin receptor made- mRNA stable
What would happen with excess iron?
Remember with excess iron, the iron binds IRP which releases IRP from binding sites

24
Q

microRNAs

A

Regulatory RNAs that regulate mRNA
Silence expression of specific mRNA targets
Bind to complementary sequences in the 3’ UT end of mRNA and degrade or block translation (depending on strength of complementary binding)

25
Q

Formation of miRNAs

A
Precursor miRNA
Cropped in nucleus
Forms double stranded loop
Further cleaved by Dicer
Joins with Argonaute and others to form RISC complex
Base pairs with mRNA
Cleaves RNA, shuts down expression
26
Q

Are changes in microRNA expression causative of disease or responsive to disease

A

Both

27
Q

Causative miRNA disease

A

Tourettes syndrome
Change in recognition sequence on target SLITRK1 mRNA–> increased miRNA binding–> decreased SLITRK1 expression–> tourettes syndrome

28
Q

3 ways to activate degredation signal

A

Phosphorylation by kinase
Unmasking by protein dissociation
Creation of destabilizing N-terminus

29
Q

Proteasome therapy

A

Proteasome inhibitors used to treat multiple myelomas
Proteasome inhibition may prevent degradation of pro-apoptotic factors for cell suicide
-leads to cell apoptosis of cancer cells

30
Q

Coordinated gene expression

A

Expression of critical regulatory protein can trigger battery of downstream genes
Example- glococorticoid hormone causes gene expression

31
Q

Decision for specialization

A

Different options for products of differentiation at each step
Example is Hematopoietic stem cells

32
Q

DNA methylation

A

Silences genes

Can be inherited

33
Q

Genomic imprinting is based on ____, Genomic imprinting definition

A

Based on DNA methylation

-Differential expression of genetic material depending on the parent of origin

34
Q

Epigenetics definition

A

Regulation of expression of gene activity without altering gene expression (e.g., methylation)

35
Q

X-chromosome inactivation

A

One X chromosome is inactivated in females by Heterochromatin- Barr Body