TY - JOUR
T1 - Epigenetic regulation of the cell type-specific gene 14-3-3σ
AU - Oshiro, Marc M.
AU - Futscher, Bernard W.
AU - Lisberg, Aaron
AU - Wozniak, Ryan J.
AU - Klimecki, Walter T.
AU - Domann, Frederick E.
AU - Cress, Anne E.
N1 - Funding Information:
Abbreviations: HMEC, human mammary epithelial cell; PrEC, prostate epithelial cell; HFF, human foreskin fibroblast Address all correspondence to: Bernard W. Futscher, Arizona Cancer Center, 1515 North Campbell Avenue, Tucson, AZ 85724. E-mail: [email protected] 1This work was supported, in part, by National Institutes of Health grants CA65662 (B.W.F.), CA73612 (F.E.D.), and CA56666 and CA75152 (A.E.C.), as well as P30 CA23074 to the Arizona Cancer Center. The Graduate Training Program in Toxicology grant ES07091 supported M.M.O. Received 21 March 2005; Revised 18 May 2005; Accepted 20 May 2005.
PY - 2005/9
Y1 - 2005/9
N2 - Epigenetic control participates in processes crucial in mammalian development, such as X-chromosome inactivation, gene imprinting, and cell type-specific gene expression. We provide evidence that the p53-inducible gene 14-3-3σ is a new example of a gene important to human cancer, where epigenetic mechanisms participate in the control of normal cell type-specific expression, as well as aberrant gene silencing in cancer cells. Like a previously identified cell type-specific gene maspin, 14-3-3σ is a p53-inducible gene; however, it participates in G2/M arrest in response to DNA-damaging agents. 14-3-3σ expression is restricted to certain epithelial cell types, including breast and prostate, whereas expression is absent in nonepithelial tissues such as fibroblasts and lymphocytes. In this report, we show that in normal cells expressing 14-3-3σ, the , 14-3-3σ CpG island is unmethylated; associated with acetylated histones, unmethylated histone H3 lysine 9; and an accessible chromatin structure. By contrast, normal cells that do not express 14-3-3σ have a methylated 14-3-3σ CpG island with hypoacetylated histones, methylated histone H3 lysine 9, and an inaccessible chromatin structure. These findings extend the spectrum of cell type-specific genes controlled partly by normal epigenetic mechanisms, and suggest that this subset of genes may represent important targets of epigenetic dysregulation in human cancer.
AB - Epigenetic control participates in processes crucial in mammalian development, such as X-chromosome inactivation, gene imprinting, and cell type-specific gene expression. We provide evidence that the p53-inducible gene 14-3-3σ is a new example of a gene important to human cancer, where epigenetic mechanisms participate in the control of normal cell type-specific expression, as well as aberrant gene silencing in cancer cells. Like a previously identified cell type-specific gene maspin, 14-3-3σ is a p53-inducible gene; however, it participates in G2/M arrest in response to DNA-damaging agents. 14-3-3σ expression is restricted to certain epithelial cell types, including breast and prostate, whereas expression is absent in nonepithelial tissues such as fibroblasts and lymphocytes. In this report, we show that in normal cells expressing 14-3-3σ, the , 14-3-3σ CpG island is unmethylated; associated with acetylated histones, unmethylated histone H3 lysine 9; and an accessible chromatin structure. By contrast, normal cells that do not express 14-3-3σ have a methylated 14-3-3σ CpG island with hypoacetylated histones, methylated histone H3 lysine 9, and an inaccessible chromatin structure. These findings extend the spectrum of cell type-specific genes controlled partly by normal epigenetic mechanisms, and suggest that this subset of genes may represent important targets of epigenetic dysregulation in human cancer.
KW - 14-3-3σ
KW - Chromatin
KW - Histone
KW - Histone acetylation
KW - Methylation
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U2 - 10.1593/neo.05274
DO - 10.1593/neo.05274
M3 - Article
C2 - 16229802
AN - SCOPUS:33644875123
SN - 1522-8002
VL - 7
SP - 799
EP - 808
JO - Neoplasia
JF - Neoplasia
IS - 9
ER -