Irradiation modulates association of NF-Y with histone-modifying cofactors PCAF and HDAC.
Post-irradiation complications including thrombus formation result from increased procoagulant activity of vascular endothelial cells and elevated levels of von Willebrand factor (VWF) contribute to this process. We have previously demonstrated that irradiation induction of the VWF is mediated through interaction of NF-Y transcription factor with its cognate binding site in the VWF promoter. We have also demonstrated that irradiation increases the association of NF-Y with histone acetyltransferase p300/CBP-associated factor (PCAF). We now report that irradiation decreases the association of NF-Y with histone deacetylase 1 (HDAC1). We demonstrate that irradiation-induced changes in association of NF-Y with HDAC1 and PCAF lead to increased PCAF recruitment to the VWF promoter, increased association of acetylated histone H4 with the VWF promoter and subsequently increased transcription. We also demonstrate that this process is correlated to dephosphorylation of HDAC1 and is inhibited by calyculin A, an inhibitor of protein phosphatase1.
Peng
Y
Y
Department of Medicine, Albert Einstein College of Medicine, Bronx, NY, USA.
Stewart
D
D
Li
W
W
Hawkins
M
M
Kulak
S
S
Ballermann
B
B
Jahroudi
N
N
D023081:CCAAT-Binding Factor / Q000378:metabolism* / Q000528:radiation effects; D002467:Cell Nucleus / Q000502:physiology / Q000528:radiation effects; D004730:Endothelium, Vascular / Q000201:enzymology / Q000502:physiology / Q000528:radiation effects*; D006655:Histone Deacetylases / Q000378:metabolism* / Q000528:radiation effects; D006657:Histones / Q000378:metabolism* / Q000528:radiation effects; D006801:Humans; D007700:Kinetics; D011401:Promoter Regions, Genetic / Q000528:radiation effects; D011485:Protein Binding; D014471:Umbilical Veins; D050880:p300-CBP Transcription Factors / Q000378:metabolism* / Q000528:radiation effects; D014841:von Willebrand Factor / Q000235:genetics; D000099224:p300-CBP-Associated Factor
D023081:CCAAT-Binding Factor; D006655:Histone Deacetylases; D006657:Histones; D050880:p300-CBP Transcription Factors; D014841:von Willebrand Factor; D000099224:p300-CBP-Associated Factor