Gene Regulation in Prokaryotes and Eukaryotes

Comprehensive vocabulary flashcards covering bacterial operons (trp and lac operons) and eukaryotic transcriptional regulation (transcription factors, HIF-1alpha, and p53).

Operon

A genetic regulatory structure in prokaryotes where a single promoter and regulatory region control the expression of multiple genes.

Polycistronic transcript

An mRNA transcript produced in prokaryotes that carries the coding sequence for multiple proteins translated from a single promoter.

Trp repressor

A regulatory protein that binds tryptophan; high tryptophan concentrations activate the repressor to bind the operator and block transcription of tryptophan-synthesizing enzymes via negative feedback.

Lac operon

A prokaryotic operon containing genes that code for the machinery to break down lactose as an alternative metabolic food source.

CAP (Catabolite Activator Protein)

A trans-acting regulatory protein that senses glucose levels; it is active and binds DNA under low glucose conditions to activate lac operon transcription.

Lac repressor

A trans-acting regulatory protein that senses lactose; it works and binds the operator under low lactose conditions, and detaches when lactose binds to it.

Operator

The cis-regulatory DNA sequence where a repressor protein binds to control the availability of the promoter to RNA polymerase.

CAP binding site

The cis-regulatory DNA sequence located near the promoter where the CAP protein binds.

Sigma subunit

A subunit required by prokaryotic RNA polymerase to identify and specifically bind to the promoter sequence.

Cyclic AMP (cAMP)

A signaling molecule produced when cellular glucose is low; it binds to the activator protein (CAP) enabling it to bind to its DNA binding site.

Specific transcription factors (STFs)

Eukaryotic regulatory proteins that bind to cis elements called enhancers to upregulate or downregulate transcription based on cellular and environmental inputs.

Enhancers

Cis-regulatory DNA sequences in eukaryotes that serve as binding sites for specific transcription factors, which can act as activators or repressors.

Mediator

A eukaryotic protein that interacts with both general transcription factors and specific transcription factors to coordinate and promote transcription initiation.

Chromatin remodeling complexes

Protein complexes recruited by activation domains to alter chromatin structure from heterochromatin to euchromatin, making the promoter accessible.

Constitutive expression

The continuous, uninterrupted production of a protein by the cell regardless of environmental conditions (seen in proteins such as HIF-1alpha and p53).

HIF-1alpha

A constitutively synthesized specific transcription factor that senses oxygen; it is degraded under normoxic conditions and stabilized under hypoxic conditions to enter the nucleus.

Hypoxia response element (HRE)

The enhancer (cis element) to which stabilized HIF-1alpha binds in the nucleus to activate target gene transcription.

PPH

An enzyme that adds hydroxyl ($\text{-OH}$) groups to HIF-1alpha under normoxic conditions, marking it for recognition by the E3 protein VHL.

VHL

An E3 ubiquitin ligase that recognizes hydroxylated HIF-1alpha under normal oxygen levels and targets it for ubiquitination and proteasomal degradation.

E3 protein

A regulatory protein in the ubiquitin-proteasome pathway that specifically selects the target protein for ubiquitination.

PDK1

A pyruvate dehydrogenase kinase upregulated by HIF-1alpha under hypoxic conditions that phosphorylates pyruvate dehydrogenase to prevent acetyl-CoA formation, driving lactic acid production.

GLUT1

A glucose transporter upregulated by HIF-1alpha in hypoxic conditions to increase glucose import across the membrane during Warburg metabolism.

p53

A critical tumor suppressor and specific transcription factor that forms a tetramer to respond to genotoxic stress, mutated in over $50\%$ of cancers.

Genotoxic stress

Cellular stress resulting from DNA damage, including double-stranded breaks, single-stranded nicks, or RNA incorporated into the DNA.

MDM2

The E3 ubiquitin ligase that binds p53 under normal conditions to mediate its ubiquitination and degradation in the proteasome.

p53 response element (p53 RE)

The cis-regulatory enhancer sequence in DNA that p53 binds to in order to drive the transcription of genes involved in DNA repair, cell cycle arrest, and apoptosis.

p21

A cell cycle regulator gene upregulated by p53 to halt cell cycle progression during DNA damage.

Bax

A pro-apoptotic gene upregulated by p53 that promotes programmed cell death under conditions such as critical telomere attrition or severe DNA damage.