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Effects of histone acetylation on transcriptional regulation of manganese superoxide dismutase gene

Author: Maehara K.   Uekawa N.   Isobe K-I.  

Publisher: Elsevier

ISSN: 0006-291X

Source: Biochemical and Biophysical Research Communications, Vol.295, Iss.1, 2002-07, pp. : 187-192

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Abstract

To better understand the link between chromatin modification and manganese superoxide dismutase (Mn-SOD) gene expression, we have investigated the level of histone acetylation at Mn-SOD proximal promoter. TSA induced the expression of Mn-SOD mRNA and its transcriptional activity in C2C12 cells. Sp1 binding sites in the proximal promoter region of Mn-SOD were transcriptionally responsive to TSA by transfection studies. We have detected a localized acetylation of histones H3 and H4, in vivo occupation by Sp1, early growth responsive-1 (Egr-1), and histone deacetylase-1 (HDAC1) in the proximal promoter region of Mn-SOD gene using chromatin immunoprecipitation assays. Our findings indicate that Mn-SOD gene expression is repressed by Sp1–HDAC1 complex. This repression is released by a localized histone acetylation and at least in parts a displacement by Egr-1 in response to TSA.© 2002 Elsevier Science (USA)