Noncooperative interactions between transcription factors and clustered DNA binding sites enable graded transcriptional responses to environmental inputs.

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-kappaB, 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-kappaB are translated into gradual increments in gene transcriptio... Mehr ...

Verfasser: Guido Tiana
Martha L. Bulyk
Luca Giorgetti
Paolo Milani
Trevor Siggers
Teresa Corona
Greta Caprara
Gioacchino Natoli
Manolis Pasparakis
Samuele Notarbartolo
Dokumenttyp: Artikel
Erscheinungsdatum: 2010
Schlagwörter: Netherlands / Biophysics
Sprache: Englisch
Permalink: https://search.fid-benelux.de/Record/base-27200571
Datenquelle: BASE; Originalkatalog
Powered By: BASE
Link(s) : https://www.openaccessrepository.it/record/135823

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-kappaB, 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-kappaB 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-kappaB-dependent promoter. We demonstrate that NF-kappaB 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.