Eukaryotic Transcription Regulation Flashcards
what determines the startpoint for transcription?
basal apparatus
what determines the frequency of transcription?
activators
coactivators
connect activators to basal factors
- some have HAT activity and connect to SWI/SNF complexes
how do repressors work in eukaryotes?
- sequestered in the cytoplasm
- concentration driven by competition
what is the role of DNA-binding domains?
to bring the transcription-activation domain into the vicinity of the promoter
- DNA binding activity and transcription-activation are carried by independent domains of an activator
transcriptional activation motifs
make contact with basal factors and recruit them to the promoter
heat shock factor DNA binding domain
- histone H1
- helix turn helix
helix-turn-helix
triple helical cluster reinforced with beta strands
- antennapedia phenotype
basic leucine zipper proteins (bZIP)
coiled-coil dimerization domain plus a basic DNA interaction domain
- GCN4
basic helix-loop-helix (bHLH)
involved in differentiation of muscle cells
zinc containing DNA binding domains
- zinc fingers
- bimetal thiolate cluster
- nuclear receptors
zinc fingers
Cys2-His 2 coordinated by a single zinc ion
- Zif268
bimetal thiolate cluster
2 zinc ions coordinated by 6 cysteines
- GAL4
nuclear receptors
- steroids and related horomones
- bind ligand to activate
- 2 zinc molecules with 4 cysteins
- gluccorticoid receptor
why do nuclear receptors have 2 zinc modules?
one for DNA interactions and the other for dimerization
how many zinc fingers fit into the major groove?
3
acidic activation domains
- cluster of negative charges
- bulky hydrophobic residues
- amphipathic
- VP16 - mammalian herpes simplex virus
what is a major class of domains found in yeast?
acidic activators
glucocorticoid receptor
across the cellular membrane and binds to the GR. This disrupts the interaction between Hsp90 and the GR and allows the hormone/receptor complex (HR) to translocate to the nucleus where it dimerizes and binds to the promoter to target genes activating transcription.
taxmoxifen
- used to fight breast cancer
- causes helix 12 to block p160 binding
ligand binding domain of the estrogen receptor
helix 12 rotates when ligand binds
- allows p160 to bind later
steroid activators
do not directly recruit members of the preinitiation
complex. Instead, they make contact with coactivatorscoactivators, which in turn,
recruit basal factors.
mode of activator function
- p160 recruits HAT activity
- the estrogen receptor first recruits the CBP in the early stages of transcription and later recruits the mediator
what do the following complexes have in common? p160, PCAF, and p300
all have HAT activity
glucocorticoid, mineralcorticoid, androgen, and progesterone
- form homodimers
- all recognize TGTTCT
- half sites are palindromes and spacing determines the element
- head to head receptors
- exception in TGACCT in estrogen
thyroid, vitamin D, retinoic acid, 9-cis-retinoic acid
- form heterodimers, with the exception of 9-cis which is a homodimer
- recognize half elements TGACCT as direct repeats
- spacing influences recognition
- head to tail
9-cis-retinoic acid spacing
1 bp
vitamin D spacing
3 bp
thyroid spacing
4bp
retinoic acid spacing
5 bp
SMRT co-repressor
- thyroid and retinoic acid receptors bind to the SMRT corepressor at the promoter in the absence of ligand
- binding reduces affinity for the corepressor and allows binding to coactivators
what triggers the glucosinolate pathway in plants?
insect feeding
glucosinolate pathway
- insect feeding
- synthesis of jasminate horomone
- activates glucosinolate pathway
- promoter repressed if no feeding, resulting in chromosome condensation and repression
- if there is feeding, Med25 and others reduce repression and start the estrogen cycle
