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Title: Structural and mechanistic insights into cooperative assembly of dimeric Notch transcription complexes

Abstract

Ligand-induced proteolysis of Notch produces an intracellular effector domain that transduces essential signals by regulating the transcription of target genes. This function relies on the formation of transcriptional activation complexes that include intracellular Notch, a Mastermind co-activator and the transcription factor CSL bound to cognate DNA. These complexes form higher-order assemblies on paired, head-to-head CSL recognition sites. Here we report the X-ray structure of a dimeric human Notch1 transcription complex loaded on the paired site from the human HES1 promoter. The small interface between the Notch ankyrin domains could accommodate DNA bending and untwisting to allow a range of spacer lengths between the two sites. Cooperative dimerization occurred on the human and mouse Hes5 promoters at a sequence that diverged from the CSL-binding consensus at one of the sites. These studies reveal how promoter organizational features control cooperativity and, thus, the responsiveness of different promoters to Notch signaling.

Authors:
; ; ; ; ; ;  [1]
  1. WU
Publication Date:
Research Org.:
Argonne National Lab. (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
Sponsoring Org.:
USDOE
OSTI Identifier:
1002864
Resource Type:
Journal Article
Journal Name:
Nat. Struct. Mol. Biol.
Additional Journal Information:
Journal Volume: 17; Journal Issue: (11) ; 11, 2010
Country of Publication:
United States
Language:
ENGLISH
Subject:
59 BASIC BIOLOGICAL SCIENCES; 99 GENERAL AND MISCELLANEOUS//MATHEMATICS, COMPUTING, AND INFORMATION SCIENCE; BENDING; DIMERIZATION; DNA; GENES; PROMOTERS; PROTEOLYSIS; SPACERS; TARGETS; TRANSCRIPTION; TRANSCRIPTION FACTORS

Citation Formats

Arnett, Kelly L, Hass, Matthew, McArthur, Debbie G, Ilagan, Ma Xenia G, Aster, Jon C, Kopan, Raphael, Blacklow, Stephen C, BWH), and DFCI). Structural and mechanistic insights into cooperative assembly of dimeric Notch transcription complexes. United States: N. p., 2010. Web. doi:10.1038/nsmb.1938.
Arnett, Kelly L, Hass, Matthew, McArthur, Debbie G, Ilagan, Ma Xenia G, Aster, Jon C, Kopan, Raphael, Blacklow, Stephen C, BWH), & DFCI). Structural and mechanistic insights into cooperative assembly of dimeric Notch transcription complexes. United States. https://doi.org/10.1038/nsmb.1938
Arnett, Kelly L, Hass, Matthew, McArthur, Debbie G, Ilagan, Ma Xenia G, Aster, Jon C, Kopan, Raphael, Blacklow, Stephen C, BWH), and DFCI). 2010. "Structural and mechanistic insights into cooperative assembly of dimeric Notch transcription complexes". United States. https://doi.org/10.1038/nsmb.1938.
@article{osti_1002864,
title = {Structural and mechanistic insights into cooperative assembly of dimeric Notch transcription complexes},
author = {Arnett, Kelly L and Hass, Matthew and McArthur, Debbie G and Ilagan, Ma Xenia G and Aster, Jon C and Kopan, Raphael and Blacklow, Stephen C and BWH) and DFCI)},
abstractNote = {Ligand-induced proteolysis of Notch produces an intracellular effector domain that transduces essential signals by regulating the transcription of target genes. This function relies on the formation of transcriptional activation complexes that include intracellular Notch, a Mastermind co-activator and the transcription factor CSL bound to cognate DNA. These complexes form higher-order assemblies on paired, head-to-head CSL recognition sites. Here we report the X-ray structure of a dimeric human Notch1 transcription complex loaded on the paired site from the human HES1 promoter. The small interface between the Notch ankyrin domains could accommodate DNA bending and untwisting to allow a range of spacer lengths between the two sites. Cooperative dimerization occurred on the human and mouse Hes5 promoters at a sequence that diverged from the CSL-binding consensus at one of the sites. These studies reveal how promoter organizational features control cooperativity and, thus, the responsiveness of different promoters to Notch signaling.},
doi = {10.1038/nsmb.1938},
url = {https://www.osti.gov/biblio/1002864}, journal = {Nat. Struct. Mol. Biol.},
number = (11) ; 11, 2010,
volume = 17,
place = {United States},
year = {Fri Nov 12 00:00:00 EST 2010},
month = {Fri Nov 12 00:00:00 EST 2010}
}