#27 Gene Regulation 2 Flashcards

1
Q

Difference between bacterialand eukaryotic gene expression

A
  1. Bacteria have one polymerase.sigma fctor guding to its promotor site while Pol II has amny polymerases

2, Eukayrotes lack operons. Each gene is sepearately regulated

  1. instead of small number of repressors and activators per gene in bacteira, euk genes are controlled by alarge nubmer of TF, soemtiems hundreds, many facotrs at at long distances
  2. Mediator
  3. DnNA is packed into chromatin to provide more opporutnies for reuglatino
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2
Q

What is Mediator?

A

central component of eukarytoic gene regulation , 24 subunit complex’ mediates communication between regulatory transcriton factors and Pol II

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3
Q

What are tewo modular designs of gene activator proteins

A
  1. dedicated to site-specific DNA recognition (DNA-binding domai)
  2. activation domain, initaites transcirtion by recruiting, oreitning and or modifying generatl TFs, Mediator and/or Pol II
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4
Q

One activator in euk can turn oN many genes

A

yup

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5
Q

What is transcriptional synergy

A

when activotrs bind simulatneously the affet is multiplicative

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6
Q

what are insulatros

A

activator preotins can act on genes a great distane away form teh enhancer binding site. This distance might be problematic b/c one activator preotine might upregualte the tx of too many gees

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7
Q

What are 4 ways that eukaryotic ACTIVATOR proteins can alter loacl structure of hromatin to enchance initiation of Tx

A
  1. ATP dependent chormatin remodeling complex decondeses the chormatin structure to make DNA more accesible
  2. histone chaperones remove some histoens tomake DNA more accessible
  3. modified histones are swapped for nmodified ones to alter the “histone code”
  4. Histone acetyltransfreases (HATs) acetylate histone tail proteins to alter the “histone code”
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8
Q

N terminal tails of histone sare accessile an reversibly modifed to regulate gene expression by activating or repressing Tx

A

yep

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9
Q

What are HATs (histone acetyltransferases)

A

they acetylate histone lysine residues

acetylation by HATs repalces positive amin gorup of LYSIN side chain with NETURAL acetyl group to reduce the positive charge of hisone particels

less positive cahrge weakens ability of histones to bend DNA–> chromatin opes up and TRANSCRIPTION IS ACTIVATED

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10
Q

what does acetyl to do histone

A

is neutralizes posiive charge to ACTIVATE trx

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11
Q

what are HDACs (histone dacetylases)

A

remove netural acetyl group form modified lysin residues, leaving bahind a positively charged amine

dacetylation by HDACs increase the positive charge of histones to help neutralize the negative chare of DNA, thereby promoting DNA benind and wrpping

TX is REPRESSED

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12
Q

does DHACs activate or rperess transctipion?

A

Repress!

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13
Q

what happens when ther eis an imbalance of acetylation and deacytlation of hisone lyine

A

luekemia, epithelial cancer, fragile X syndeom ,Rbuinstein Tyabi sydro e

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14
Q

what are two toher reversible modifeicaiton

A

Ser/Tyr phosphyrtlin and dephosphyorylation as well as Lys methyaltino adn demethylation

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15
Q

What are 6 ways to repress eukaryotic gene transcription

A
  1. competitve DNA binding
  2. masing the activation surface (repressor binds to sbidn site as well as activator)
  3. direct interaction of repressor with TF
  4. recrutiement of chromatin remodeling complexes
  5. recruitment of hisotne dacetyalses
  6. recrutiemten of histone methyl transferases
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16
Q

what will happen if repressor protein recruites hisont deactylases

A

represses transcritpion

17
Q

what happens when hisont methytransfeases recruites

A

recruits proteins that maintin chromatin in a trascriptionally silent form

Lysing and arg residues are methylated

18
Q

what amino acids are methylates on histones

A

Lys and Arg

19
Q

Diff between HLH homodimer and heterodimer? which one is active?

A

Homodimer- 2 intact proteins and ACTIVE

heterodimer- one shorter b/c DA recognition helix was delted

20
Q

what is Ey

A

master regulator

21
Q

what is NF-kb

A

regualtes >400 genes

linked with inflammatory diseases, cacer, pumonary, autoimmune, skin ,enruodegeneative CV,

22
Q

what is epigenetics?

A

affects phenotype without changing genotype

23
Q

what are 4 different epigenetic modifiecations?

A
  1. protein A is a regulator portien taht actiates its own expression
  2. Methylation of DNA is maintatined after DNA replication (so trais CAN be inherited)
  3. chroamtin has its histones methylated –> pretins that recognize histone code help keep it transcriptiaonlly SILENT

these sites of odification rerut reaer write complees that resore local hormatin reigon to sam leel of modifiaction that was fodn in parent chormatin region

  1. Aggregated proteins have two fomers

fucntional form and aggreated form which causes disease–> aggregated forms polymer and can be inherited

24
Q

what dos DNA methylation do to transcription

A

it represses transcritpion

silecne a gene or region of chromatin

doesnt affect geomtry of CG pair

accessible for preotien recognition but doenst interfere with base pair fomration

25
what are sits of methyaltion
not isoalted GC pairs but a symmetric pair of base pairs , CG pair followed by GC pair ensures methyaltion is restored tot eh copied strand after DNA replciation SYMMETRIC PAIR of CG repeats CG GC
26
What is Fragile X syndrome? Molecular basis
insertion of variable length in the 5'UTR fo the FMR1 gene, which is an RNA binding protein expected to tplay a role in mRNA transprot triple repate expansion of cGG in the 5'UTR repeats form 50-200 x and leads to hypermethyltion of DNA, which in turn recruits specific proteins These proteins recruite HDACs with condense choratin to repress Tx
27
what region is affected by Prader-wWilli Syndrome and Angelman syndrome?
15q11 - q13 (chromsoomes 15 at loci 11-13)
28
what about impritnign
maternal alleles are differntially methyalted relative to paternal counterpart, leading to differenes in protein and snoRNA expression
29
producitno of gametes?
female gametes, the paternal DNA is methylated during production of male gametes, maternal DNA imprint is erased (demethylated)
30
which copy was delted in Prader Willi Syndrome
Paternal yto genetic deletion, offspring don't express several improtnat proteins and small nucleolar RNAs PATERNAL COPY DELETED maternal copies are repressed by DNA methylation
31
Which copy is deleted in Angelman's syndrome
metrnal cytogenetic dletion offspring don't express several importnat preotoins b/c maternal copy has been delted and paternal alleles are repressed by production of antisense RNA even thugh several genes are delted, UBE3A gene which is a ubiquitin ligase E3A, causes Angelman syndrom loss of fucniton of UBE3a