Controle of Gene Expression (8) Flashcards
housekeeping genes
expressed in all cells all the time, routine functions
What are 3 conditions that cause certain gene expression?
cell begins to differentiate
cells with specialized functions
conditions change
regulatory sequences
DAN which through the action of specific PROs control the activity/expression of genes
PRO coding
upstream
diffs in regulatory genes among species
where are regulatory sequences located in respect to a gene?
upstream
What are the diff levels/way that genes are regulated?
transcription
processing
translational
post translational
transcription level regulation
o if & how often a gene is transcribed
One gene can be transcribed more than another, rate of transcription
processing level regulation
o diff mRNAs made from a given gene
Stored or translated immediately
translational level
how much of the mRNA is made into PRO (mRNA lifetime)
post-translation
PRO lifetime
What causes RNA pol II to transcribe some genes more than others?
regulatory sites on the DNA & presence of transcription factors
transcription factors & what domains are assoc with the PRO?
DNA-binding PROS that regulate transcription
DNA binding domain activation domain (binding site for other PROs) binding site for a second subunit to form a dimer
What regulatory PROs are dimers? (2)
helix-loop-helix motif & leucine-zipper motif
what PROs are involved in regulating gene expression?
zinc-finger motif
helix loop helix motif
leucine zipper motif
zinc finger motif
multi finger-shaped projections of PRO fit into major grooves of DNA
ONLY monomers enables fitting into grooves
helix loop helix motif
produce transcription factors, homo & heterodimers
Functions as a dimer
leucine zipper motif
2 helices zipped together, binds to small region of DNA
Dimer
what regulatory PRO contains helices
leucine zipper motif
where is the core promoter located in respect to the gene?
-1 to -40 bases from the start codon
upstream
what does RNA pol I require to bind to genes?
transcription factors
what recognizes the core promoter?
DNA binding PROs: general transcription factors comprising of the pre-initiation complex
TBP: recognizes TATA 30 bases upstream
TAF: grp of general transcription factors PROs for RNA pol II
RNA pol II: produces the RNA
What PROs are apart of the pre-initiation complex?
TBP
TAF
RNA pol II
TBP
recognizes the TATA sequences 30 bases upstream from the start gene
pre-initiation complex & core promoter
TAFs
a grp of general transcription factors PROs necessary for pol II
pre-initiation complex & core promoter
RNA Pol II
produces RNA
positions RNA pol to being process
pre-initiation complex & core promoter
What complex is required to start expression?
pre-initatiation complex
proxmial promoter
- 40 to -150 bases away
CAAT & GC boxes bind to transcription factors such as NF1 which recruits a co-activator needed for Pol I to work
also recruits general transcription factors
What is the role of NF1?
binds to CAAT & GC boxes to recruit a co-activator required for RNA pol to work
what does the proximal promoter regulate?
frequency of transcription
what does the core promoter regulate?
whether or not transcription can occur
how is the proximal promoter inactivated?
cytoseins in the GC box are methylated
gene is transcriptionally inactive
distal promoter
-500 to - 100 bp
contains response elements
response elements
DNA sequence that binds to PROs called specific transcription factors recruit transcription factors such as, HLH, zinc finger etc.
specific transcription factors
activate or repress transcription activity to a specific gene or multiple genes
what are the 3 promoters?
core promoter
proximal promoter
distal promoter
how is gene activity regulated?
presence or absence of specific transcription factors
how are transcription factors activated?
dimerization
how does the proximal promoter end transcription?
transcription factors recruit repressors
proximal promoter can control the ____ & ____ of transcription
rate & frequency
enhancers
specific DNA sequences found far from the target gene that bind to specific transcriptional activators & activate gene expression
up or down stream
what do enhancers recruit to activate gene expression
specific transcription factors
insulator sequences
separate enhancers from each other by binding to PROs that separate loops
use of structural DNA
How do steroids regulate gene expression? Use the ex of Glucocorticoid receptor that controls expression of PEPCK gene.
- Glucocorticoid (cortisol) is released from the adrenal gland
- Passes through liver membrane
- Binds to receptor, receptor changes shape
- NLS expressed allowing entry into nucleus
- Receptor with bound hormone binds to a response element, which binds as a dimer & transcription of PEPCK begins newly made RNA leaves the nucleus
- PEPCK PRO made glycogenesis begin
How does cortisol trigger the repair of damaged tissue?
rapid production of sugar
DNA binding domain
recognizes a specific DNA sequence
Dimer therefore, recognizes a palindronic sequence
What recognizes a palindromic sequence?
DNA binding domain
activation domain
alters transcription usually through a co-repressor or co-activator
how does the glucocorticoid receptor turn on the gene?
brings in coactivators that:
supply general transcription factors for RNA pol II, TAFs
& alter chromatin binding structure
How do transcription factors affect gene transcription?
alter histone-binding PRO making the gene accessible to RNA pol
&
acetyl grps –> enable loosening of DNA allowing the transcription factors to have access
How does a specific transcription factor work?
binds to the response elements in the distal promoter region
recruits co-activator PROs which help the pre-initiation complex work, binds transcription factors & modifies histones
acetyl transferases –> opens up & alters activity
enhances the RNA pol activity
What are the aspects of a coactivator?
“mediator” + histone modifying enzyme + xhromatin remodeling complex
what do coactivators link transcription factors to?
general transcription factors needed for transcription
chromatin re modeling enzymes
what is the coactivator for the glucocorticoid receptor called?
CBP coactivator
a type of histone acetyltransferase (HAT)
What does CBP do to histones & what 2 effects does it have?
acetylates the lysine residues of histones exposing TATA boxes. TAFII250 acetylates histones as RNA transcribes
reduces strength of histone-DNA interaction
reduces the interactions b/w the histone PROs
What complex has its own histone acetyltransferase activity?
preinitiation complex
histone deacetylases (HDACs) & what effect does it have on gene activity?
remove acetyl grps & DNA winds up more tightly
gene activity is silences
histone methyltransferases & what effect does it have on gene activity?
methyl grps added to histones cause tighter binding
gene activity is silences
DNA methyltransferases
add methyl grps to DNA at C 5 of cytosine
what happens if a cytosine is methylated in a GC Box?
silenced forever
“tags” regions of DNA so that they’re utilized (transcribed) differently
reversible process but methylation is “passed on”
what are the 3 enzymes involved in transcriptional repression?
histone deacetylases (HDACs)
histone methyltransferases
DNA methyltransferases
