Cell and Molec Ch 18: Regulation of Gene Expression
post-transcriptional regulation
RNA processing, lifespan of mRNA, protein processing/degradation, RNA interference
operon
a group of genes that operate together according to common function; consists of a promoter and genes
bacterial DNA
genes for common functions grouped together in operons
transcription factories
genes with related functions able to congregate in interphase nucleus; sites rich in RNA polymerase and other transcription-associated proteins, helps coordinately control dispersed genes
specific transcription factors
interact with gene-specific control elements, required for high levels of transcription; activators and repressors
CAP (catabolite activator protein)
lac activator; made in inactive form, activates when bound to cAMP
differentiation
process by which cell attains its determined fate, becomes a specific cell type
lifespan of mRNA
persistence of eukaryotic mRNA influences how much of mRNA product gets produced
determination
point at which an embryonic cell is irreversibly committed to a particular cell type; genes for tissue-specific proteins give cell a characteristic structure
mRNA breakdown
poly A tail enzymatically broken down, which triggers removal of 5' cap --> nuclease enzymes can then degrade mRNA
sequential regulation of gene expression
precursor cells (determination) --> determined cells (differentiation) --> differentiated cell (specific cell type)
tryptophan NOT present in abundance (repressible)
regulatory gene makes inactive repressor; operator of operon is ON, enzymes to make tryptophan are made
negative gene regulation
regulatory protein a repressor, blocks transcription when active; lac operon and trp operon
positive gene regulation
regulatory protein an activator, initiates transcription when active; lac operon ONLY
control elements
segments of noncoding DNA that help regulate transcription by binding certain proteins; only about 10-12, but make unique combos
enhancers
segments to eukaryotic DNA containing multiple control elements; unique due to combinations of control elements
lac operon
under both negative and positive gene regulation
histone modification
acetylation leads to looser DNA structure, promotes transcription; methylation leads to condensed DNA structure, reduces transcription
hormone receptors
act as transcription factors (bind to promoters) for coordinately controlled genes on different chromosomes
general transcription factors
act at promoter of all genes, essential for all protein-coding genes
protein degradation
after translation; ubiquitin (recycling) tag added to protein --> degraded in proteasome (enzymatic complex) --> protein fragments recycled
lactose present (inducible)
allolactose binds to repressor and inactivates it; operator now ON (just a little); genes that break down lactose are made *operon induced by presence of substrate*
signals in early development
cytoplasmic determinants, inductive signals; tell cell which genes to turn on/off (yields cells with different properties)
glucose absent, lactose present
decrease in glucose and ATP lead to increase in cAMP, CAP activator now active; CAP binds to promoter, RNA pol can bind (a lot); operon turned ON, genes that break down lactose are made
euchromatin
10-30 nm; accessible to machinery for transcription (looser structure)
heterochromatin
300 nm; not accessible to machinery for transcription (too dense)
regulation of chromatin structure
DNA methylation and histone modification
promoter
RNA polymerase binding site + operator (on/off switch)
DNA-bending proteins
brings bound activators in contact with mediator proteins; help to assemble transcription initiation complex, bending helps enhancers to influence promoter
transcription initiation complex
cluster of proteins that assembles on the promoter; allows RNA pol II to bind and transcribe gene; general + specific transcription factors, mediator proteins, DNA-bending proteins
eukaryotic genomes
compared to prokaryotes, are much larger, more complex, spread out amongst multiple chromosomes and do NOT group genes in operons
enzymes that digest glucose
consituitive (always present)
tryptophan
end product of enzymes made from trp operon, acts as a corepressor
differential gene expression
expression of different sets of genes by cells with the same genome; why there are differences between cell types
glucose and lactose BOTH present
glucose used so that energy saved (no need to make enzymes for lactose) CAP activator inactive, RNA pol cannot bind, genes that break down lactose not expressed at high level
coordinate control
in eukaryotes, hormones and transcription factories coordinate genes with related functions that are spread out along different chromosomes
mediator proteins
interact with activators at the promoter
lac operon on completely
inactive repressor is on, active activator is on
enzymes that digest lactose
inducible, costs energy to make them
proximal control elements
located close to the promoter
DNA methylation
methyl group added to a base (often cytosine); condenses DNA structure, reduces transcription
distal control elements
more distant from promoter, groupings called enhancers
constituitive enzymes
needed all the time, produced all the time
regulator genes
not part of operon, but help control it; make a regulatory protein (repressor/activator) that binds to operator, turn operon off/on
RNA processing (alternative RNA splicing)
one gene can splice in different ways and thus express different proteins; more than one mRNA (and therefore protein) possible
eukaryotic gene
promoter, introns + exons (gene), poly-A signal, proximal control elements, enhancer (~10 distal control elements)
lactose absent (inducible)
repressor stays active, operator stays OFF; structural genes not transcribed
gene expression
requires RNA polymerase to find the correct gene
regulation of metabolic pathways
saves energy by making enzymes only when needed (regulating enzyme production/gene expression)
RNA interference (RNAi)
small single-stranded molecules (miRNA + siRNA) control gene expression by binding to mRNA and interfering with translation (prevents attachment of ribosomes)
repressors
specific transcription factors that decrease gene expression, repress gene activity
activators
specific transcription factors that increase rate of transcription; bind to proximal and distal (enhancer) control elements
genes of the operon
structural genes that code for proteins
inducible enzymes
transcription usually off, but can be turned on (induced) by the presence of their substrate (i.e., lac operon)
repressible enzymes
transcription usually on, but can be turned off (repressed )by the end product they make (i.e., feedback inhibition)
tryptophan IS present in abundance (repressible)
tryptophan binds to inactive repressor and activates it; active repressor binds to operator, turns it OFF; genes of operon NOT expressed, more tryptophan NOT made
cytoplasmic determinants
unevenly distributed substances in fertilized egg (e.g., mRNA, proteins) that influence which genes are on/off; distributed into dividing cells differently, yielding cells with different developmental fates
inductive signals
via paracrine signaling, specific transcription factors are activated in receiving cell --> influence gene regulation in receiving cell, affect its developmental fate
cancer
when gene regulation goes wrong