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AP Biology. Lecture #35 Gene Regulation. Positive gene control. occurs when an activator molecule interacts directly with the genome to switch transcription on.

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ap biology

AP Biology

Lecture #35

Gene Regulation

positive gene control
Positive gene control
  • occurswhen an activator moleculeinteracts directly with the genome to switch transcription on.
  • Even if the lac operon is turned on by the presence of allolactose, the degree of transcription depends on the concentrations of other substrates.
  • The cellular metabolism is biased toward the utilization of glucose.
positive gene regulation
Positive Gene Regulation
  • Some operons are also subject to positive control through a stimulatory protein, such as catabolite activator protein (CAP), an activator of transcription
  • When glucose (a preferred food source of E. coli) is scarce, CAP is activated by binding with cyclic AMP
  • Activated CAP attaches to the promoter of the lac operon and increases the affinity of RNA polymerase, thus accelerating transcription
positive gene regulation1
Positive Gene Regulation
    • If glucose levels are low (along with overall energy levels), then cyclic AMP(cAMP) binds to cAMP receptor protein (CRP) which activates transcription.
  • If glucose levels are sufficient and cAMP levels are low (lots of ATP), then the CRP protein has an inactive shape and cannot bind upstream of the lacpromotor.
the big questions
The BIG Questions…
  • How are genes turned on & off in eukaryotes?
  • How do cells with the same genes differentiate to perform completely different, specialized functions?
evolution of gene regulation
Evolution of gene regulation
  • Prokaryotes
    • single-celled
    • evolved to grow & divide rapidly
    • must respond quickly to changes in external environment
      • exploit transient resources
  • Gene regulation
    • turn genes on & off rapidly
      • flexibility & reversibility
    • adjust levels of enzymes for synthesis & digestion
evolution of gene regulation1
Evolution of gene regulation
  • Eukaryotes
    • multicellular
    • evolved to maintain constant internal conditions while facing changing external conditions
      • homeostasis
    • regulate body as a whole
      • growth & development
        • long term processes
      • specialization
        • turn on & off large number of genes
      • must coordinate the body as a whole rather than serve the needs of individual cells
points of control
Points of control
  • The control of gene expression can occur at any step in the pathway from gene to functional protein

1. packing/unpacking DNA

2. transcription

3. mRNA processing

4. mRNA transport

5. translation

6. protein processing

7. protein degradation

1 dna packing as gene control
1. DNA packing as gene control
  • Degree of packing of DNA regulates transcription
    • tightly wrapped around histones
      • no transcription
      • genes turned off
  • heterochromatin

darker DNA (H) = tightly packed

  • euchromatin

lighter DNA (E) = loosely packed



dna methylation
DNA methylation
  • Methylation of DNA blocks transcription factors
    • no transcription

 genes turned off

    • attachment of methyl groups (–CH3) to cytosine
      • C = cytosine
    • nearly permanent inactivation of genes
      • ex. inactivated mammalian X chromosome = Barr body
histone acetylation
Histone acetylation
  • Acetylation of histones unwinds DNA
    • loosely wrapped around histones
      • enables transcription
      • genes turned on
    • attachment of acetyl groups (–COCH3) to histones
      • conformational change in histone proteins
      • transcription factors have easier access to genes
epigenetic inheritance
Epigenetic Inheritance
  • Although the chromatin modifications just discussed do not alter DNA sequence, they may be passed to future generations of cells
  • The inheritance of traits transmitted by mechanisms not directly involving the nucleotide sequence is called epigenetic inheritance
2 transcription initiation
2. Transcription initiation
  • Control regions on DNA
    • promoter
      • nearby control sequence on DNA
      • binding of RNA polymerase & transcription factors
      • “base” rate of transcription
    • enhancer
      • distant control sequences on DNA
      • binding of activator proteins
      • “enhanced” rate (high level) of transcription
model for enhancer action
Model for Enhancer action
  • Enhancer DNA sequences
    • distant control sequences
  • Activator proteins
    • bind to enhancer sequence & stimulates transcription
  • Silencer proteins
    • bind to enhancer sequence & block gene transcription

Turning on Gene movie

transcription complex
Transcription complex

Activator Proteins

• regulatory proteins bind to DNA at distant enhancer sites

• increase the rate of transcription

Enhancer Sites

regulatory sites on DNA distant from gene









RNA polymerase II




Coding region


Core promoter

and initiation complex

Initiation Complex at Promoter Site binding site of RNA polymerase


Fig. 18-9-3





Distal control










Group of

mediator proteins


polymerase II


polymerase II


initiation complex

RNA synthesis

3 post transcriptional control
3. Post-transcriptional control
  • Alternative RNA splicing
    • variable processing of exons creates a family of proteins
4 regulation of mrna degradation
4. Regulation of mRNA degradation
  • Life span of mRNA determines amount of protein synthesis
    • mRNA can last from hours to weeks

RNA processing movie

5 control of translation
5. Control of translation
  • Block initiation of translation stage
    • regulatory proteins attach to 5' end of mRNA
      • prevent attachment of ribosomal subunits & initiator tRNA
      • block translation of mRNA to protein

Control of translation movie

6 7 protein processing degradation
6-7. Protein processing & degradation
  • Protein processing
    • folding, cleaving, adding sugar groups, targeting for transport
  • Protein degradation
    • ubiquitin tagging
    • proteasome degradation

Protein processing movie


1980s | 2004

  • “Death tag”
    • mark unwanted proteins with a label
    • 76 amino acid polypeptide, ubiquitin
    • labeled proteins are broken down rapidly in "waste disposers"
      • proteasomes

Aaron Ciechanover


Avram Hershko


Irwin Rose

UC Riverside

  • Protein-degrading “machine”
    • cell’s waste disposer
    • breaks down any proteins into 7-9 amino acid fragments
      • cellular recycling

play Nobel animation

concept 18 3 noncoding rnas play multiple roles in controlling gene expression
Concept 18.3: Noncoding RNAs play multiple roles in controlling gene expression
  • Only a small fraction of DNA codes for proteins, rRNA, and tRNA
  • A significant amount of the genome may be transcribed into noncoding RNAs
  • Noncoding RNAs regulate gene expression at two points: mRNA translation and chromatin configuration
rna interference


RNA interference
  • Small interfering RNAs (siRNA)
    • short segments of RNA (21-28 bases)
      • bind to mRNA
      • create sections of double-stranded mRNA
      • “death” tag for mRNA
        • triggers degradation of mRNA
    • cause gene “silencing”
      • post-transcriptional control
      • turns off gene = no protein produced


action of sirna

Hot…Hotnew topicin biology

Action of siRNA


mRNA for translation


double-stranded miRNA + siRNA



mRNA degraded

functionally turns gene off


Gene Regulation



protein processing & degradation

1 & 2. transcription

- DNA packing

- transcription factors

3 & 4. post-transcription

- mRNA processing

- splicing

- 5’ cap & poly-A tail

- breakdown by siRNA

5. translation

- block start of translation

6 & 7. post-translation

- protein processing

- protein degradation



initiation of translation




initiation of transcription

mRNA protection


mRNA splicing


molecular biology of cancer
Molecular Biology of Cancer
  • Oncogene •cancer-causing genes
  • Proto-oncogene •normal cellular genes
  • How? 1-movement of DNA; chromosome fragments that have rejoined incorrectly 2-amplification; increases the number of copies of proto-oncogenes
  • 3-proto-oncogene point mutation; protein product more active or more resistant to degradation
  • Tumor-suppressor genes •changes in genes that prevent uncontrolled cell growth (cancer growth stimulated by the absence of suppression)
cancers result from a series of genetic changes in a cell lineage
Cancers result from a series of genetic changes in a cell lineage
  • The incidence of cancer increases with age because multiple somatic mutations are required to produce a cancerous cell
  • As in many cancers, the development of colon cancer is gradual