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