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21 fall: Biochem > lecture 9 > Flashcards

lecture 9 Flashcards

1
Q

your patient is severely anemic and has essentially no B-globin protein or RNA. There is no mutation within the B-globin gene
What is the defect?

A

deletion of the B-globin locus control region

B-thalassemia

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2
Q

Cleft palate

A

sequence variants in the transcription factors IRF6, PVRL1, MSX1

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3
Q

white coat

A

mutation in a gene on the S locus encoding transcription factor MITF

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4
Q

Canine Burkitt Lymphoma

Cause?

A

chromosomal translocation of the c-Myc transcription factor gene into the IgH locus causing dysregulation of c-Myc expression

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5
Q

TADs

A

topological associated domains

organize genome
usually active

regulatory loops
sub-TADs -enhancers and promoters

long distance DNA interactions by architectural loops

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6
Q

subTAD

A

brings together enhancer that binds transcription factors and bind them to a promoter

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7
Q

histone code terms

A

histone modification writes
histone modification erasers
histone modification readers

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8
Q

examples of histone modification writers

A

acteylases (make less + add Ch3-C=0)
methy-transferases (add CH3)
kinases (add phosphate)

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9
Q

examples of histone modification erasers

A

deacteylases
demethylases
phosphatases

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10
Q

examples of histone modification readers

A

proteins with bromodomains
-see acetylated histones
proteins with chromodomains
-see methylated histones

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11
Q

activation histone code signals

A

H3K4me3
H3K9ac
H3K14ac

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12
Q

repression histone mode signals

A

H3K9me3

H3K27me3

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13
Q

HDAC inhibitors and therapy

A

histone deacetylase
leads to silencing- turn off gene

inhibiting these will turn on genes

depsipeptide-CLL and T cell lymphoma
MS-275
SAHA
Depudesin (reverses transformation of NIH3T3 cells)

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14
Q

if C followed by a G

CpG

A

DNA is methylated
transcription is off

involved in DNA imprinting during development- different methylated groups go on and off as organism develops

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15
Q

locus control regions now called ____

A

super enhancers

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16
Q

super enhancers or locus control regions are

A

regions of the genome that control very large sections of the genome

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17
Q

example of deletion of an LCR

A

LCR deleted upstream from B-globin locus.

patients get B-thalassemia

18
Q

spot on gene that help polymerase to bind

A

TATA box

19
Q

what binds to TATA box

A

general transcription factors attach to TATA
(TBP, TAFs) TF 11D
TF-IIA
TF-IIB

TFIID- binds along with other complexes
TF-IIA stabilizes the complex on DNA
TF-IIB helps position RNA polymerase to the right start site

20
Q

___ directs RNA Polymerase II to attach

A

general transcription factors specifically TF-IIB

21
Q

three types of coactivators

A

mediators
-bridges activators, GFT, RNA polymerase

Swi/Snf- has ATPase activity that remodels chromatin (makes things move over to allow transcription)

histone modification enzymes
-HAT/HDAC/Methyltransferase

22
Q

example of mediator coactivators

A

bridges activators between transcription factors and RNA polymerase

23
Q

example of Swi/Snf

A

ATPase that remodels chromatin

24
Q

example of Histone Modification Enzymes

A

HAT/HDAC/Methyltransferase
(acetylation, deacetylation, methylation)

(covalently modify histones and other proteins

25
Q

carboxy terminal Domain

A

CTD

largest subunit of RNA polymerase II

repeated sequence of specifically amino acids that repeat 27-52 times

(have hydroxyl groups(OH)
sites of phosphorylation (add P with 4 O/phosphate)) tyr-ser-pro-thr-ser-pro-ser

TF-IIH is believed to phosphorylate CTD

26
Q

TF-IIH

A

kinase that adds phosphate to CTD and tells RNA polymerase it is time to bind

TF-IIH (XPB and XPD) is from NER
(nucleotide excision repair) that causes unwinding of DNA (helicase)

27
Q

transcription factors will

A

bind to specific DNA sequences.

control the level of transcription either activate or repress expression.

can be thousands of base pairs away

there are 1000s of transcription factors

28
Q

there are two parts of transcription factors

A

DNA binding domain- bind to DNA and interact with the basal complex to stabilize TFIID binding to the TATA

transcriptional activation domain
-interact with coactivators to increase TFIID binding and RNA polymerase recruitment.

29
Q

types of DNA binding domains

A 
zinc fingers
homeodomains
leucine zipper and basic region
helix-loop helix and basic region
Ets domain
Fork head
Rel
30
Q

leucine zippers deal with

A

dimerization domains

control bone formation, cell growth

31
Q

homeodomains deal with

A

development

can create bithorax (double wings)

32
Q

type os activation domains

A

acid blobs
proline rich
glutamine

33
Q

HAT vs HDACs

A

there are retinoic acid receptors in the cell

if RAR bind with retinoic acid(RA) then RAR binds with HAT- transcription on

if RAR does not bind with RA then RAR binds with HDAC- transcription off

histone acetyltransferase activity (HAT)
bind with retinoic acid and add histone acetyl marks which activates transcription

histone deacetylase (HDACs)
separate from retinoic acid and removes histone acetyl marks and represses transcription
34
Q

HAT

A

type of coactivators

histone acetyltransferase activity (HAT)

bind with retinoic acid and add histone acetyl marks which activates transcription

35
Q

HDACs

A

histone deacetylase (HDACs)

separate from retinoic acid and removes histone acetyl marks and represses transcription

36
Q

Swi/Snf

A

type of coactivators

push nucleosomes

this allows TATA to be exposed
allows transcription

37
Q

mediator

A

type of coactivators

acts as bridge between transcription factors and RNA polymerase

this stabilizes everything at promotor so gene expression can go on

38
Q

how are gene regulation controlled

A

regulators can be present in single tissue types

multiple dimerization partners

post-translational modifications

combinatorial assortment of binding proteins

39
Q

how do flies get stripes

A

bicoid expresses stripes

hunchback and knirps are repressors of bicoid

when neither hunchback or knirps are expressed then you get a stripe (kruppel)

40
Q

example of tissue differentiation regulated by dimer formation in muscle development

A

MyoD-E2A heterodimer= muscle development

MyoD-Id heterodimer= no muscle

cell types can be triggered by transcription factors into another cell type
(change cell into other cell)

41
Q

explain how gene regulatory networks could be used in medicine

A
  1. activate lineage-specific gene regulatory networks
  2. turn off broken one
  3. make sure you did the right thing and didn’t change something else accidentally
42
Q

*** transcription factor activation domains can stimulate transcription. Describe several ways that these domains can function

A

activation domains such as acid blobs, proline rich or glutamine rich act to bridge information/relay between general transcription factors and DNA binding domain of transcription factors. they can also act to bring proteins to the transcription area. such proteins may act to speed up the initiation or process of transcription. activation domains may also communicate with co-activators such as mediators, swi/snf and HAT. Activation domains may also function to specifically expedite the entrance of RNA polymerase to the TFIID or even to expedite the binding of TFIID to DNA

Bind to DNA and interact with the basal complex to stablilize GFTs (TFIID) binding.

interact with coactivator (mediators, Swi.Snf and HAT/HDAC/Methyltransferase) to increase TFIID binding and RNA polymerase II recruitment

21 fall: Biochem (44 decks)

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