TY - JOUR
T1 - Transcriptional co-activators CREB-binding protein/p300 increase chondrocyte Cd-rap gene expression by multiple mechanisms including sequestration of the repressor CCAAT/enhancer-binding protein
AU - Imamura, Toshihiro
AU - Imamura, Chisako
AU - Iwamoto, Yukihide
AU - Sandell, Linda J.
PY - 2005/4/29
Y1 - 2005/4/29
N2 - Cartilage-derived retinoic acid-sensitive protein (CDRAP) is a small secreted matrix protein expressed in developing and adult cartilage and by chondrocytes in culture. We have previously shown that the expression of Cd-rap, like many other cartilage matrix proteins, is repressed by interleuldn 1β and that the transcription factor CCAAT/enhancer-binding protein (C/EBP) β plays an important role in the interleukin 1β-induced repression (Okazald, K., Li, J., Yu, H., Fukui, N., and Sandell, L. J. (2002) J. Biol. Chem. 277, 31526-31533). The coactivators CREB-binding protein (CBP) and p300 are transcriptional co-regulators that participate in the activities of many different transcription factors including C/EBP. Here we show that CBP/p300 can reverse the inhibitory effect of C/EBP and moreover can stimulate expression of Cd-rap. The mechanism of this effect is shown to involve a unique synergy whereby CBP/p300 stimulate Cd-rap gene expression by at least two mechanisms. First, binding of CBP/p300 to C/EBPβ leads to sequestration of C/EBP eliminating DNA binding and subsequent repression; second, binding of CBP/p300 to the transcriptional activator Sox9 increases Sox9 DNA binding to the Cd-rap promoter leading to further stimulation of gene transcription. This is an example of a complementary transcriptional network whereby two very different mechanisms act together to confer a functional increase in transcription. This new paradigm is likely generally applicable to cartilage genes as Col2a1 cartilage collagen gene responds similarly.
AB - Cartilage-derived retinoic acid-sensitive protein (CDRAP) is a small secreted matrix protein expressed in developing and adult cartilage and by chondrocytes in culture. We have previously shown that the expression of Cd-rap, like many other cartilage matrix proteins, is repressed by interleuldn 1β and that the transcription factor CCAAT/enhancer-binding protein (C/EBP) β plays an important role in the interleukin 1β-induced repression (Okazald, K., Li, J., Yu, H., Fukui, N., and Sandell, L. J. (2002) J. Biol. Chem. 277, 31526-31533). The coactivators CREB-binding protein (CBP) and p300 are transcriptional co-regulators that participate in the activities of many different transcription factors including C/EBP. Here we show that CBP/p300 can reverse the inhibitory effect of C/EBP and moreover can stimulate expression of Cd-rap. The mechanism of this effect is shown to involve a unique synergy whereby CBP/p300 stimulate Cd-rap gene expression by at least two mechanisms. First, binding of CBP/p300 to C/EBPβ leads to sequestration of C/EBP eliminating DNA binding and subsequent repression; second, binding of CBP/p300 to the transcriptional activator Sox9 increases Sox9 DNA binding to the Cd-rap promoter leading to further stimulation of gene transcription. This is an example of a complementary transcriptional network whereby two very different mechanisms act together to confer a functional increase in transcription. This new paradigm is likely generally applicable to cartilage genes as Col2a1 cartilage collagen gene responds similarly.
UR - http://www.scopus.com/inward/record.url?scp=20444444670&partnerID=8YFLogxK
U2 - 10.1074/jbc.M411469200
DO - 10.1074/jbc.M411469200
M3 - Article
C2 - 15722556
AN - SCOPUS:20444444670
SN - 0021-9258
VL - 280
SP - 16625
EP - 16634
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 17
ER -