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High throughput resequencing to characterize age associated changes in nuclear factor erythroid 2 related factor 2 and the antioxidant response element interactions
Author(s) -
Smith Eric Jonathan,
Hagen Tory M
Publication year - 2009
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.23.1_supplement.855.6
Subject(s) - gclc , gclm , transcription factor , chromatin immunoprecipitation , nrf1 , glutathione , biology , response element , chemistry , promoter , genetics , microbiology and biotechnology , gene , protein subunit , biochemistry , enzyme , gene expression
Interaction between Nuclear factor erythroid 2 related factor 2 (Nrf2,) a transcription factor, and all the classes of antioxidant response element (ARE) regulate important bioremediation of xenobiotics and reactive oxygen species. Nuclear levels of Nrf2 declines with age, as does its binding to a consensus ARE sequences. The glutamate‐cysteine ligase catalytic subunit (GCLC) gene is a quintessential Nrf2/ARE regulated gene that contains several AREs and codes for an enzyme essential for glutathione synthesis. We have previously shown that Nrf2 displays differential binding to the GCLC promoter at various AREs with age and that this change results in a decline in glutathione synthesis. Chromatin Immunoprecipitation (ChIP) coupled with qPCR has been a useful tool in defining the interactions between Nrf2 and the AREs in the GCLC promoter. Here ChIP has been coupled with high throughput resequencing (ChIP‐seq) to examine genome wide ARE and Nrf2 interaction in liver tissue isolated from young and old male F344 rats. Results show a dramatic change in the transcription factor binding profile between the two experimental groups.