Display Settings:

Format

Send to:

Choose Destination
See comment in PubMed Commons below
J Biol Chem. 2001 Dec 14;276(50):47296-302. Epub 2001 Oct 2.

Spatially precise DNA bending is an essential activity of the sox2 transcription factor.

Author information

  • 1San Raffaele Scientific Institute, via Olgettina 58, 20132 Milan, Italy.

Abstract

Sox proteins, a subclass of high mobility group box proteins, govern cell fate decisions by acting both as classical transcription factors and architectural components of chromatin. We aimed to demonstrate that the DNA bending activity of Sox proteins is essential to regulate gene expression. We focused on mouse Sox2, which participates in the transactivation of the Fgf4 (fibroblast growth factor 4) gene in the inner cell mass of the blastocyst. We generated six substitutions in the high mobility group box of Sox2. One mutant showed a reduced DNA bending activity on the Fgf4 enhancer (46 degrees instead of 80 degrees), which resulted in more powerful transactivation compared with the wild type protein. We then selected two single-base mutations in the Fgf4 enhancer that make the DNA less bendable by the Sox2 protein. Again, a different DNA bend (0 degrees and 42 degrees instead of 80 degrees) resulted in a different activation of transcription, but in this case reduced bending corresponded to decreased transcription. We found that the opposite effect on transcription of similar DNA bending angles is due to a 20 degrees difference in the relative orientation of the DNA bends, proving that a correct three-dimensional geometry of enhanceosome complexes is necessary to promote transcription.

PMID:
11584012
[PubMed - indexed for MEDLINE]
Free full text
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Icon for HighWire
    Loading ...
    Write to the Help Desk