c-Myc mediates a hypoxia-induced decrease in acetylated histone H4.
Global acetylation of histone H4 is a mark of gene transcriptional activation. The c-Myc transcription factor binds to specific DNA sites in cellular chromatin and induces the acetylation of histone H4. In this study, hypoxia (1% Oxygen) induced a decrease in both global acetylated histone H4 (AcH4) and c-Myc in human lung carcinoma A549 cells and in human bronchial epithelial Beas-2B cells, The decline was more striking in A549 cells compared to Beas2-B cells, when cells were exposed to hypoxic stress for 24 h. Further studies showed that these alterations of global AcH4 can be attributed to the decrease in c-Myc protein levels. While hypoxia-induced gene activation is known to be mediated by Hypoxia Response Elements (HRE), the mechanism for down-regulation of genes by hypoxia is not known. The decrease in c-Myc protein levels induced by hypoxia may contribute to hypoxia-induced gene repression.
Li
Qin
Q
New York University School of Medicine, Nelson Institute of Environmental Medicine, Tuxedo, NY 10987, USA.
Costa
Max
M
D000107:Acetylation; D015153:Blotting, Western; D015687:Cell Hypoxia / Q000502:physiology*; D002460:Cell Line; D045744:Cell Line, Tumor; D006657:Histones / Q000378:metabolism*; D006801:Humans; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism*
D006657:Histones; D016271:Proto-Oncogene Proteins c-myc