Noncooperative Interactions between Transcription Factors and Clustered DNA Binding Sites Enable Graded Transcriptional Responses to Environmental Inputs

Luca Giorgetti, Trevor Siggers, Guido Tiana, Greta Caprara, Samuele Notarbartolo, Teresa Corona, Manolis Pasparakis, Paolo Milani, Martha L. Bulyk, Gioacchino Natoli

Research output: Contribution to journalArticlepeer-review

Abstract

A paradigm in transcriptional regulation is that graded increases in transcription factor (TF) concentration are translated into on/off transcriptional responses by cooperative TF binding to adjacent sites. Digital transcriptional responses underlie the definition of anatomical boundaries during development. Here we show that NF-κB, a TF controlling inflammation and immunity, is conversely an analog transcriptional regulator that uses clustered binding sites noncooperatively. We observed that increasing concentrations of NF-κB are translated into gradual increments in gene transcription. We provide a thermodynamic interpretation of the experimental observations by combining quantitative measurements and a minimal physical model of an NF-κB-dependent promoter. We demonstrate that NF-κB binds independently to adjacent sites to promote additive RNA Pol II recruitment and graded transcriptional outputs. These findings reveal an alternative mode of operation of clustered TF binding sites, which might function in biological conditions where the transcriptional output is proportional to the strength of an environmental input.

Original languageEnglish
Pages (from-to)418-428
Number of pages11
JournalMolecular Cell
Volume37
Issue number3
DOIs
Publication statusPublished - Feb 12 2010

Keywords

  • DNA
  • SYSBIO

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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