Abstract
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.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 50 print issues and online access
$259.00 per year
only $5.18 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Adachi N, Nomoto M, Kohno K, Koyama H . (2000). Cell-cycle regulation of the DNA topoisomerase IIalpha promoter is mediated by proximal CCAAT boxes: possible involvement of acetylation. Gene 245: 49–57.
Barford D, Das AK, Egloff MP . (1998). The structure and mechanism of protein phosphatases: insights into catalysis and regulation. Annu Rev Biophys Biomol Struct 27: 133–164.
Bertagna A, Jahroudi N . (2001). The NFY transcription factor mediates induction of the von Willebrand factor promoter by irradiation. Thromb Haemost 85: 837–844.
Brush MH, Guardiola A, Connor JH, Yao TP, Shenolikar S . (2004). Deactylase inhibitors disrupt cellular complexes containing protein phosphatases and deacetylases. J Biol Chem 279: 7685–7691.
Caretti G, Salsi V, Vecchi C, Imbriano C, Mantovani R . (2003). Dynamic recruitment of NF-Y and histone acetyltransferases on cell-cycle promoters. J Biol Chem 278: 30435–30440.
Criswell T, Leskov K, Miyamoto S, Luo G, Boothman DA . (2003). Transcription factors activated in mammalian cells after clinically relevant doses of ionizing radiation. Oncogene 22: 5813–5827.
Dichek D, Quertermous T . (1989). Variability in messenger RNA levels in human umbilical vein endothelial cells of different lineage and time in culture. In Vitro Cell Dev Biol 25: 289–292.
Edwards E, Geng L, Tan J, Onishko H, Donnelly E, Hallahan DE . (2002). Phosphatidylinositol 3-kinase/Akt signaling in the response of vascular endothelium to ionizing radiation. Cancer Res 62: 4671–4677.
Fajardo LF . (1996) In: Waksman R, King SB, Crocker IR, Mould RF (eds.) Vascular Brachytherapy. Nucletron BV, Veenendaal: The Netherlands, 74.
Guo C, Mi J, Brautigan DL, Larner JM . (2006). ATM regulates ionizing radiation-induced disruption of HDAC1:PP1:Rb complexes. Cell Signal 19: 504–510.
Guo CY, Brautigan DL, Larner JM . (2002). Ionizing radiation activates nuclear protein phosphatase-1 by ATM-dependent dephosphorylation. J Biol Chem 277: 41756–41761.
Hu Z, Jin S, Scotto KW . (2000). Transcriptional activation of the MDR1 gene by UV irradiation. Role of NF-Y and Sp1. J Biol Chem 275: 2979–2985.
Ishihara H, Martin BL, Brautigan DL, Karaki H, Ozaki H, Kato Y et al. (1989). Calyculin A and okadaic acid: inhibitors of protein phosphatase activity. Biochem Biophys Res Commun 159: 871–877.
Jahroudi N, Lynch DC . (1994). Endothelial-cell-specific regulation of von Willebrand factor gene expression. Mol Cell Biol 14: 999–1008.
Jin S, Fan F, Fan W, Zhao H, Tong T, Blanck P et al. (2001). Transcription factors Oct-1 and NF-YA regulate the p53-independent induction of the GADD45 following DNA damage. Oncogene 20: 2683–2690.
Jin S, Scotto KW . (1998). Transcriptional regulation of the MDR1 gene by histone acetyltransferase and deacetylase is mediated by NF-Y. Mol Cell Biol 18: 4377–4384.
Maity SN, de Crombrugghe B . (1998). Role of the CCAAT-binding protein CBF/NF-Y in transcription. Trends Biochem Sci 23: 174–178.
Manni I, Mazzaro G, Gurtner A, Mantovani R, Haugwitz U, Krause K et al. (2001). NF-Y mediates the transcriptional inhibition of the cyclin B1, cyclin B2, and cdc25C promoters upon induced G2 arrest. J Biol Chem 276: 5570–5576.
Mantovani R . (1998). A survey of 178 NF-Y binding CCAAT boxes. Nucleic Acids Res 26: 1135–1143.
Mantovani R . (1999). The molecular biology of the CCAAT-binding factor NF-Y. Gene 239: 15–27.
Peng Y, Jahroudi N . (2002). The NFY transcription factor functions as a repressor and activator of the von Willebrand factor promoter. Blood 99: 2408–2417.
Peng Y, Jahroudi N . (2003). The NFY transcription factor inhibits von Willebrand factor promoter activation in non-endothelial cells through recruitment of histone deacetylases. J Biol Chem 278: 8385–8394.
Rodeghiero F . (2002). Von Willebrand disease: still an intriguing disorder in the era of molecular medicine. Haemophilia 8: 292–300.
Weichselbaum RR, Hallahan D, Fuks Z, Kufe D . (1994). Radiation induction of immediate early genes: effectors of the radiation-stress response. Int J Radiat Oncol Biol Phys 30: 229–234.
Acknowledgements
This work was supported by research grant HL-67729 (NJ) of the National Institute of Health.
Author information
Authors and Affiliations
Corresponding author
Additional information
Supplementary Information accompanies the paper on the Oncogene website (http://www.nature.com/onc).
Supplementary information
Rights and permissions
About this article
Cite this article
Peng, Y., Stewart, D., Li, W. et al. Irradiation modulates association of NF-Y with histone-modifying cofactors PCAF and HDAC. Oncogene 26, 7576–7583 (2007). https://doi.org/10.1038/sj.onc.1210565
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/sj.onc.1210565
Keywords
This article is cited by
-
Association of p21 with NF-YA suppresses the expression of Polo-like kinase 1 and prevents mitotic death in response to DNA damage
Cell Death & Disease (2014)
-
Interaction of C/EBP-beta and NF-Y factors constrains activity levels of the nutritionally controlled promoter IA expressing the acetyl-CoA carboxylase-alpha gene in cattle
BMC Molecular Biology (2012)
-
ATM-dependent IGF-1 induction regulates secretory clusterin expression after DNA damage and in genetic instability
Oncogene (2011)
-
Histone deacetylase inhibitors induce FPGS mRNA expression and intracellular accumulation of long-chain methotrexate polyglutamates in childhood acute lymphoblastic leukemia: implications for combination therapy
Leukemia (2010)
-
PCAF lysine acetyltransferase
AfCS-Nature Molecule Pages (2008)
