Regulation Of Eukaryotic Gene Expression Flashcards
Site for regulation of gene expression
. Transcription control . Processing of primary transcript . RNA transport . Translational control . Posttransitional control
Two levels of gene expression control
. Conversion of compacted chromatin to an extended structure (activation)
. Fine-tuning of transcription mediated by DNA-binding proteins/transcription factors (modulation)
Types of transcription factors
. General transcription factors: abundant proteins that assemble on all genes transcribed by RNA polymerase II
. Gene regulatory proteins/specific transcription factors: proteins present in few copies in individual cells, perform functions by binding to DNA-specific nucleotide sequence, allows genes that they control to be activated or repressed
Transcription factors structure
. Bind DNA as homo or heterodimers
. Contain unique structural motifs w/ precise AA sequence that determines particular DNA sequences that are recognized
Transcription factors are important for ___
. Issue specific expression
. Cell growth and differentiation
. Lipid soluble soluble hormones bind their cognate receptors to regulate transcription in target cells
The absolute rate that a gene is transcribed is regulated by ____
Number of polymerase that are synthesizing RNA from the gene sequence
. Transcription factors modulate this
Domains in regulatory proteins that activate transcription
. Modular design
. One domain w/ structural motif that recognized specific DNA sequences
. Domain that contacts transcriptional machinery and accelerates rate of transcription initiation by accelerating assembly of general transcription factors at promoter site
Transcriptional control of erythropoietin gene
. Hypoxia inducible factor (HIF) bind hypoxia response element (HRE) in gene in hypoxic conditions
. HIF-1alpha (only present in hypoxia) and beta (always present) make dimer at HRE site after alpha moves into nucleus
. Result is upregulation of EPO gene expression
How is HIF-1alpha degraded in normal oxygen conditions?
. Normally hydroxylated via prolyl hydroxylase
. Causes binding of E3 ubiquitin ligase (VHL protein)
. Resulting polyubiquination caused by its degradation by the proteasome
Alternative Splicing
. Ability of genes to form multiple proteins by joining different exon segments in primary transcript
. Happens by RNA binding proteins changing the accessibility of different splicing sites by masking a site or changing the local RNA structure to promote splicing of alternate sites
. Explains why genome Harper genes than there are proteins
Alternative splicing in calcitonin gene
. In thyroid cells, cleavage of transcript to make calcitonin occurs at polyA site 1
. In brain, same transcript that makes calcitonin undergoes alternative splicing to produce calcitonin-gene related protein that cleaves at poly A site 2 (site 1 is masked by transcription factor proteins)
T/F majority of nuclear RNA is degraded by nucleases before they move into cytoplasm for translation
T, helps prevent inappropriate gene expression
Steady state of individual RNA species in a cell is determined by ____
Rate of transcription and rate of decay
Stability of mRNA is influenced by signals inherent in ____
The 3’ untranslated region (UTR) and poly A tail
How 3’ UTR influences stability of mRNA?
. 3’ UTR sequences form stem-loop structure for protein-binding and protection from degradation
