J Mol Biol. 1961 Jun;3:318-56. Genetic regulatory mechanisms in the - - PowerPoint PPT Presentation

j mol biol 1961 jun 3 318 56 genetic regulatory
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J Mol Biol. 1961 Jun;3:318-56. Genetic regulatory mechanisms in the - - PowerPoint PPT Presentation

J Mol Biol. 1961 Jun;3:318-56. Genetic regulatory mechanisms in the synthesis of proteins ( Or the Operon Theory ) Franois JACOB & Jacques MONOD The Operon Model, Jacob & Monod, 1961 Lac & bacteriophage lambda induction lacI


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J Mol Biol. 1961 Jun;3:318-56. Genetic regulatory mechanisms in the synthesis of proteins (Or the Operon Theory) François JACOB & Jacques MONOD

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The Operon Model, Jacob & Monod, 1961

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Lac & bacteriophage lambda induction

lacI promoter

  • perator

lac Z RNA polymerase lacI promoter

  • perator

lac Z RNA polymerase REPRESSED INDUCED mRNA repressor inducer cI promoter

  • perator

Lytic RNA polymerase cI promoter

  • perator

RNA polymerase REPRESSED INDUCED mRNA repressor Lytic UV radiation

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RNAP a subunit consists of two domains connected by a long, flexible linker.

The a N-terminal domain (aNTD) interacts with RNAP b and b' subunits. The a C-terminal domain (aCTD) interacts with CAP and with DNA.

R.Ebright lab Cell 78:889, 1994

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Determination of an EM structure of the intact CAP-RNA Polymerase-promoter complex.

  • R. Ebright lab PNAS 106:1, 2009
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Transcription activation by two independent activators

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  • Transcription regulation in bacteria,

extensions

  • Negative and positive regulators
  • Several regulators for a single gene
  • DNA bending to facilitate contacts
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Systems biology in bacteria

Can we describe a bacterial life cycle? The caulobacter’s asymmetric cell division Harley McAdams & Lucy Shapiro

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Flexible design for genetic subsystem control

Time

Mod Mod Mod CtrA Mod Mod GcrA DnaA

Cyclical regulatory protein concentrations activate and repress modular subsystems Feedback and checkpoints add additional synchronization controls

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Going from bacteria to nucleated eucaryotes

  • Site of transcription is distinct from that of protein synthesis
  • Compaction of DNA in nucleosomes and higher order

structures: Chromatin

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Minichromosome of SV40 Gilles Moyne et al,1981

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The nucleosome and the tails of histones

H2A yellow; H2B red; H3 blue; H4 green, T.Richmond et al

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Chromatin, DNA compaction and gene regulation

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Elements of eukaryotic transcriptional control

Diversity of Coregulators Mediator

Mediator

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The AP1 transcription factor

A dimer of cJun and cFos A paradigm for eucaryotic TFs

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Transcriptional induction of cJun mRNA in the absence

  • r presence of protein synthesis inhibitor

Protein induced specifically binds to 5’ TGACTCA

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Negative feed back loops in gene activation

  • D. Bohmann
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Kinetics of Jun proteins induction by serum growth factors