#27 Gene Regulation 2 Flashcards Preview

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Flashcards in #27 Gene Regulation 2 Deck (31):
0

Difference between bacterialand eukaryotic gene expression

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

3. 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

4. Mediator

5. DnNA is packed into chromatin to provide more opporutnies for reuglatino

2

What is Mediator?

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

3

What are tewo modular designs of gene activator proteins

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

4

One activator in euk can turn oN many genes

yup

5

What is transcriptional synergy

when activotrs bind simulatneously the affet is multiplicative

6

what are insulatros

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

7

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

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"

8

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

yep

9

What are HATs (histone acetyltransferases)

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

10

what does acetyl to do histone

is neutralizes posiive charge to ACTIVATE trx

11

what are HDACs (histone dacetylases)

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

12

does DHACs activate or rperess transctipion?

Repress!

13

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

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

14

what are two toher reversible modifeicaiton

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

15

What are 6 ways to repress eukaryotic gene transcription

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

16

what will happen if repressor protein recruites hisont deactylases

represses transcritpion

17

what happens when hisont methytransfeases recruites

recruits proteins that maintin chromatin in a trascriptionally silent form

Lysing and arg residues are methylated

18

what amino acids are methylates on histones

Lys and Arg

19

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

Homodimer- 2 intact proteins and ACTIVE

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

20

what is Ey

master regulator

21

what is NF-kb

regualtes >400 genes
linked with inflammatory diseases, cacer, pumonary, autoimmune, skin ,enruodegeneative CV,

22

what is epigenetics?

affects phenotype without changing genotype

23

what are 4 different epigenetic modifiecations?

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

4. Aggregated proteins have two fomers

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

24

what dos DNA methylation do to transcription

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