• Gene Regulation: control of the rate and timing of gene expression

• there are controls that regulate gene expression at every point in the transition from DNA to final protein

• Places where gene expression is regulated:

  1. transcription

  2. post-transcriptional processing: if pre-mRNA is processed quickly, final protein produced quickly

  3. translation: mRNA is more likely to be translated when ribosomes have greater affinity for it

  4. post-translational processing: if the immature protein is processed quickly, the final functional protein can work sooner

Prokaryotes vs Eukaryotes:

• prokaryotes: smaller number of controls for multiple protein coding structures

• eukaryotes: large number of controls for a single protein coding gene

Gene Regulation in Prokaryotes:

1. through allosteric regulation of enzymes themselves: feedback inhibition

2. through the regulation of the expression of the genes that encode enzymes

• constitutive genes: always on, expressed all the time

• inducible genes: only expressed when the proteins they produce are required by the cell

Kinds of Gene Regulation:

• negative regulation: presence of a repressor at the binding site inhibits transcription and the removal it promotes transcription

• positive regulation: presence of an activator at the binding site promotes transcription and its removal inhibits transcription

  • lac operon: produces enzymes involved in a catabolic pathway (breakdown of lactose) inducible operon, negative control

  • trp operon: produces enzymes in the synthesis of tryptophan, repressible operon, negative control

The Lac Operon:

• inducible operon

• structural gene: proteins not involved in gene regulation

• regulatory gene: proteins such as transcription factors that are directly involved in gene regulation

• lac operon is off by default

• lacI gene produces a repressor that is usually active which binds to the activator, preventing RNA polymerase from binding to the promoter

• turned on when lactose is present

• remains off if lactose is present if glucose is present as well

• when glucose is not present, E coli produces cAMP as an activator of the lac operon

• cAMP binds to and activates CAP (catabolite activator protein)

• when glucose is present, E coli do not produce cAMP, and CAP remains inactive and do not bind

Lac Operon Summary:

• strong transcription when lactose is present and glucose is absent

• very low (basal) transcription when both lactose and glucose are present

• no transcription if lactose is not present

Trp Operon:

• repressible operon: on by default, can be turned off by presence of regulatory protein

• gene expression in trp operon is on by default and can be turned off by presence of tryptophan

• Sigma factor: protein found in bacteria that directs RNA polymerase to specific promoters, controlling initiation of transcription and gene expression

Regulating Eukaryotic Gene Expression:

• prokaryotes: functionally related genes grouped into operons, only one RNA polymerase, fewer promoters, transcription begins with simple binding of RNA polymerase

• eukaryotes: distant from one another, with separate promoters, 3 RNA polymerase (transcribes rRNA, transcribes mRNA, transcribes tRNA and small RNAs), far more promoters, RNA polymerase and several other proteins must bind to the promoter to initiate transcription

Regulation of Transcription:

• general transcription factors

• specific transcription factors

• regulatory proteins (activators and repressors)

  • activators bind to enhancers

  • repressors bind to silencers

Epigenetic Changes:

• temporary and reversible changes but are heritable

  • chromatin remodeling via histone modification