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Decreased Phosphorylation of Histone H3 serine 10 by Genistein is Associated with the Transcriptional Upregulation of ATF3 in DLD‐1 Colon Cancer Cells
Author(s) -
Zhang Yukun,
Strakovsky Rita S.,
Chen Hong,
Pan Yuan-Xiang
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.969.6
Subject(s) - chromatin immunoprecipitation , atf3 , activating transcription factor , phosphorylation , histone h3 , histone , promoter , chemistry , downregulation and upregulation , microbiology and biotechnology , kinase , transcription factor , mapk/erk pathway , biology , gene expression , gene , biochemistry
Activating transcription factor 3 (ATF3) is transcriptionally regulated by a variety of bioactive compounds during carcinogenesis. The present study investigated the mechanisms behind the regulation of ATF3 gene expression by genistein (GEN), a soy isoflavone, in DLD‐1 colon cancer cells. We examined the effect of GEN on histone modifications and the binding of transcription factors within the ATF3 promoter using Chromatin immunoprecipitation (ChIP). GEN upregulated ATF3 mRNA expression and the extra‐cellular signal regulated kinase (ERK) in a time‐dependent manner. Inhibition of ERK phosphorylation by U0126 did not abolish GEN‐induced ATF3 upregulation. However, GEN repressed the phosphorylation of Jun‐N‐terminal kinase (JNK). Inhibiting the phosphorylation of JNK (pJNK) by SP600125 resulted in increased ATF3 mRNA, indicating that JNK negatively regulated its expression. GEN reduced the phosphorylation of histone H3 at serine 10 (pH3S10), and the JNK inhibitor experiment confirmed that this was due to the reduction of pJNK. The GEN‐induced increase of ATF3 promoter activity was associated with decreased pH3S10 and increased ATF2 binding at the promoter. Our results indicate that GEN reduces pH3S10 at the promoter of an actively transcribed gene, providing a promising direction for investigating GEN‐mediated gene regulation and its role in colon carcinogenesis.