Regulation of Gene Expression Flashcards
What is LRP5?
LDL receptor-related protein 5
What is BMP4?
bone morphogenetic protein 4
What is IRF6?
interferon-regulatory factor 6
What is GRHL3?
grainyhead-like 3
What is AMOT?
angiomotin
What is a gene?
a segment of DNA that is transcribed into RNA
-associated regions that control how, when, where, and in what amount RNA is transcribed
What is the central dogma?
DNA>RNA> protein
Are all genes expressed in all cell types?
no
-only housekeeping genes are on in every cell
Why is gene regulation important?
-determines how a cell can take on specialized functions
-determines how a cell responds to environmental change or external stimuli
-determine maintenance of tissue homeostasis
-morphogenesis (growth & shape change)
-cell communication (response to signals from neighboring cells)
-evolutionary adaptation (changes in gene regulation can lead to new traits)
-immune responses
What are promoters and transcriptional start sites?
TATA box- helps position RNA polymerase
What are enhancers?
function far from transcription start site but enhance gene expression
What are silencer/repressor elements?
opposite of enhancer function
What are response elements?
specific sequences within enhancers and silencers that respond to signaling pathways and environmental cues
What are insulators? (boundary elements)
act as barriers to restrict action of enhancers/silencers to particular genes
What are CpG islands?
stretches of DNA sequences that have a content of CpG dinucleotides (cytosine followed by guanine)
cytosine bases in these islands are often targeted for methylation (type of epigenetic modification)
-control gene expression
What are the general requirements of gene expression control?
core transcriptional machinery (ex: RNA polymerase)
What are the specific requirements of gene expression control?
-intracellular hormone-receptor complexes
-intracellular second messenger
-gene specific transcription factors
-gene regulatory sequences
What are some examples of proteins that are involved with gene expression?
-activation/coactivator
-repressor/ corepressors
-mediators and DNA binding proteins
-chromatin remodeling proteins
-histone acetylase/deactelyase
-histone methylation
-DNA methylation
How does DNA exist in the cell?
it exists as a highly condensed nucleosome form with numerous associated proteins
What are histones?
highly basic proteins that bind to DNA
-five families: H1/H5 (linker), H2-H4 (core)
-abundant in arginine and lysine amino acids
-act as dynamic spools for DNA, creating nucleosomes
-control transcription factors access to gene regulatory elements
How many times does DNA wind around histones?
1.65 times
disruption of histones=
disruption of gene expression
What are the modifications of histone tails possible?
-acetylation
-methlyation
-phosphorylation
*controls TF interaction
what does histone methylation do to gene expression?
blocks the association of enzymes and blocks the activation of gene expression
What are characteristics of DNA?
-right handed helix
-minor and major grooves
What is helix-loop-helix motif?
common in transcription factors and consists of alpha helices bound by a looping stretch of amino acids
What are Zinc-finger motifs?
bind to DNA and have zinc metal ions associated with the protein
-some have an alpha helix plus beta sheet structure, others have a more helix-turn-helix structural motif
-can be monomers or dimers
What is a helix-turn-helix motif?
DNA binding motif consisting of two alpha helices joined by a short stretch of amino acids
-homeobox proteins
What is a leucine zipper motif?
two proteins each with an alpha helix formed a Y shaped coiled-coil structure
-results in both protein and DNA binding
Where does the alpha helix bind to DNA?
major groove
-residues in recognition alpha helix bond with certain bases in the DNA
-HTH proteins function as dimers, so require optimal DNA sequence in both major groove
What does a leucine zipper do?
promote dimerization and DNA binding
What are nuclear hormone receptors?
important class of transcription factors activated by ligand
-endogenous hormones, sterols, vitamin A, vitamin D, and xenobiotics
-often contain two zinc fingers, that recognize a bipartite sequence
-ligand binding can stabilize/initiate interaction with other TFs
what do protein motifs look for in minor and major grooves to know where to bind?
hydrogen atoms and methyl groups
Class I nuclear hormone receptors
ligand bound in cytosol –> complex moves to nucleus
Class II nuclear hormone receptors
ligand enter nucleus to bind receptors on DNA
Do transcription factors act alone?
no
-partners enhance stability of interaction with DNA
-co-operative binding requires nearby recognition sites for each TF
What do promoters do?
help to define the transcription start site
-position the RNA polymerase
Are enhancers/silencers always close to the start site?
no, they can be 5’ of promoter, 3’ of flanking regions, and introns
What is the TATA box?
located 25-30 bp of 5’ start site, binds TBP subunit TFIID
What is the INR?
initiator
-contains the start site of transcription for RNA polymerase II genes
-bind TFIID
What is the DPE?
downstream promoter element
-located at +30 of the start site, binds TFIID
What is the BRE?
TFIIB-recognition element
-located at -35 of the start site, binds TFIIB
When are chromosomes less packed?
when undergoing mitosis
What allows enhancers and promoters to come together?
extracellular stimuli of cells expressing appropriate transcription factors
-assembly of transcriptional complexes
Does transcriptional activation occur at one spot at a time?
no, occurs at hundreds of genes at once
What does the gene expression program dictate?
cellular response and alters cellular and tissue phenotype
Is gene expression controlled only by tissue type?
no, it is also controlled by timing
-if genes are on at wrong times, there can adverse affects
What do mutations in Wnt10a cause?
oligodontia/hypodontia
What do mutations in Wnt9b cause?
cleft lip/palate
Is gene expression regulated at one level?
no, there are many levels of regulation for gene expression
