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Papers In Press, published online ahead of print January 2, 2003
J. Biol. Chem, 10.1074/jbc.M213156200
Submitted on December 23, 2002
Revised on January 2, 2003
Accepted on January 2, 2003

The NFY transcription factor inhibits VWF promoter activation in non-endothelial cells through recruitment of histone deacetylases

Yiwen Peng and Nadia Jahroudi

Medicine, Division of Cardiology, Albert Einstein College of Medicine, Bronx, NY 10461

Corresponding Author: ypeng{at}aecom.yu.edu

Human Von Willebrand factor (VWF) gene sequences +155 to +247 contain cis-acting elements that contribute towards endothelial specific activation of the VWF promoter. Analyses of this region demonstrated the presence of a GATA binding site that is necessary for the promoter activation in endothelial cells. We have recently reported the presence of a novel NFY binding sequence in this region that does not conform to the consensus NFY binding sequence CCAAT. NFY was shown to function as a repressor of the VWF promoter through interaction with this novel binding site. Here we report that the NFY interacts with histone deacetylases (HDACs) in a cell-type specific manner and recruits them to the VWF promoter to inhibit the promoter activity in non-endothelial cells. Analyses of the acetylation status of histones in the chromatin region containing the VWF promoter sequences demonstrated that these sequences are associated with acetylated histone H4 specifically in endothelial cells. It was also demonstrated that HDACs are specifically recruited to the same chromatin region in non-endothelial cells. We also demonstrated that GATA6 is the GATA family member that interacts with the VWF promoter and that GATA6 is associated with NFY specifically in non-endothelial cells. We propose that NFY recruits HDACs to the VWF promoter, which may result in deacetylation of GATA6 as well as of histones in non-endothelial cells, thus leading to promoter inactivation. In endothelial cells however, association of HDACs, NFY and GATA6 is interrupted potentially through endothelial-cell specific signaling/mechanism, thus favoring the balance towards acetylation and activation of the VWF promoter.


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