TY - JOUR
T1 - Spatially Precise DNA Bending Is an Essential Activity of the Sox2 Transcription Factor
AU - Scaffidi, Paola
AU - Bianchi, Marco E.
PY - 2001/12/14
Y1 - 2001/12/14
N2 - 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° instead of 80°), 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° and 42° instead of 80°) 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° difference in the relative orientation of the DNA bends, proving that a correct three-dimensional geometry of enhanceosome complexes is necessary to promote transcription.
AB - 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° instead of 80°), 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° and 42° instead of 80°) 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° difference in the relative orientation of the DNA bends, proving that a correct three-dimensional geometry of enhanceosome complexes is necessary to promote transcription.
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U2 - 10.1074/jbc.M107619200
DO - 10.1074/jbc.M107619200
M3 - Article
C2 - 11584012
AN - SCOPUS:0035861642
VL - 276
SP - 47296
EP - 47302
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
SN - 0021-9258
IS - 50
ER -