Prokaryotic Gene Regulation

Prokaryotic Gene Regulation

PROKARYOTIC GENE REGULATION

  • Cell must be able to respond to changes in environment

OPERON model-

  • Related genes grouped together with single “on-off” switch called an OPERATOR
  • PROMOTOR- region where RNA polymerase binds to start transcription
  • REGULATORY GENE farther away makes REPRESSOR that binds to operator to control binding of RNA polymerase

INDUCIBLE OPERON- Example: Lactose (lac) operon

  • Operon is TURNED OFF
  • REPRESSOR is in ACTIVE FORM unless INDUCER (lactose) is present

–usually functions in catabolic pathways to digest nutrients into simpler

–cell avoids making proteins that have nothing to do

–cell allocates resources to other uses

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REPRESSIBLE OPERON- Example: Tryptophan (trp) operon

  • Operon is TURNED ON
  • REPRESSOR is in INACTIVE FORM unless COREPRESSOR (tryptophan) is present

–usually functions in anabolic pathwayssynthesizing end products

–when end product is present in excess, cell allocates resources to other uses

EUKARYOTIC DNA STRUCTURE

LEVELS OF DNA PACKING REGULATE GENE EXPRESSION
DNA packaged in chromatin fibers- regulates access to DNA by RNA
polymerase

NUCLEOSOMES- made of DNA wrapped around 8 HISTONE proteins

HETEROCHROMATIN-tightly packed/no transcription

EUCHROMATIN- loosely packed/transcription

Acetylation (-COCH3) of histones unwraps DNA

NUCLEOSOMES→ FIBERS→LOOPED DOMAINS→ CHROMOSOMES

EPIGENETIC INHERITANCE –
inheritance not carried by nucleotide sequence
Genomic imprinting-methylation of DNA bases inactivates genes

EX: Angelman’s (maternal) & Prader Willi (paternal) syndromes

All cells have ALL GENES-

Cell specialization (differentiation)= result of different cells turning on/off different genes (ACTIVATORS/REPRESSORS)

POST TRANSCRIPTIONAL REGULATION OF GENE EXPRESSION

  • ALTERNATIVE RNA PROCESSING- different mRNA’s can be made by editing same transcript depending on which parts are treated as introns/exons
  • mRNA DEGRADATION- siRNA’s (small interfering)- bind to mRNA and degrade it
  • INITIATION OF TRANSLATION-regulatory proteins can prevent attachment of ribosomes
  • PROTEIN PROCESSING/DEGRADATION-control activation and degradation of proteins

UBIQUITIN protein- tags proteins for destruction

PROTEASOMES-recognize ubiquitin tags and digest tagged proteins

Genes=only ~3% of human genome

  • protein-coding sequences (1%)
  • non-protein coding genes (2%) -tRNA’s, rRNA’s, siRNA’s

Most of DNA (97%) does not code for protein-

  • regulatory sequences- promoters, enhancers, terminators
  • “junk” DNA
  • Introns
  • repetitive DNA (centromeres, telomeres, tandem & interspersed repeats)

Ex: Fragile X syndrome – CGG repeats in promoter region on X chromosome
most common cause of inherited mental retardation

Ex: Huntington’s- CAG repeats produces mutant Huntingtin protein that causes neurological damage

  • transposons – 1st discovered by Barbara McClintock in corn

segments of DNA that move within genome; function unknown

Ex: Alu in humans (10% of human genome)

  • retrotransposons- segments move with help of RNA intermediates and reverse transcriptase coded for by retrotransposon (may be source of retroviruses)

Many genes exist in MULTIGENE FAMILIES-

Can be collections of identical or similar genes

EX: genes for rRNA subunits

Can be different-

EX: HEMOGLOBIN-multiple chains coded for on different chromosomes; used at different times

(Fetal hemoglobin is different from adult hemoglobin)

PSEUDOGENES-nonfunctional sequences similar to functional genes

Can be used to determine evolutionary relationships

EX: Humans and other primates have nonfunctional pseudogene for vitamin C production

70% of the almost 100 different odor receptor genes are nonfunctional in humans

HOMEOTIC GENES- control overall body plan in plants and animals by regulating development

1st discovered as fruit fly mutants with body parts in wrong places

Highly conserved (few mutational changes)

Called HOX genes in animals

EUKARYOTIC GENE REGULATION
No OPERONS-individual genes PROMOTOER still binds RNA POLYMERASE

Regulatory sequences near or far from gene control its expression

  • TATA BOXES within PROMOTER region help RNA polymerase attach
  • ENHANCER REGION upstream bends; ACTIVATORS help RNA Polymerase attach
  • Numerous other proteins TRANSCRIPTION FACTORS/MEDIATORS also involved
  • SPECIFIC TRANSCRIPTION FACTORS (activators and repressors) in each kind of cell determine which genes are expressed (Ex: ALBUMIN made in liver cell; CRYSTALLIN made in eye lens cell)

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