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Potential role of distal regulatory elements in ubiquitous induction of the calcitonin/calcitonin gene‐related peptide (CALCA) gene in sepsis
Author(s) -
Park Ki Youb,
Russo Andrew
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.660.9
Subject(s) - gene , biology , gene expression , microbiology and biotechnology , in silico , genetics
The CALCA gene is expressed only in neuroendocrine tissues in a normal condition but it is ubiquitously induced in a septic condition. So far, the molecular mechanism underlying the tissue‐wide induction of the CALCA gene is unknown. Here, I identified DNA regulatory elements that might mediate the abnormal induction of the CALCA gene using adipocytes as a model system. Using a web‐based "evolutionary conserved region (ECR)" browser, I found two ECRs (ECR2 and ECR3) at the 3' end of the CALCA gene. Both ECRs were conserved among mammals, marsupial and bird. ECR2 showed a moderate enhancer activity at a basal condition in CALCA expressing cell line, CA77. ECRs were then, delivered to adipocytes through virus. Treatment of pro‐inflammatory agents increased activity of these virally delivered ECRs in adipocytes, but not in CA77 and Rat2 cells. This supports that ECRs might be involved in the inflammation‐caused CALCA gene induction. Furthermore, I found that ECR2 and ECR3 were bound by acetylated histone H3 independently of pro‐inflammatory stimuli. In silico analysis of the ECR2 sequence provided a putative binding site of hepatocyte nuclear factor (HNF)‐1. This study is the first attempt to identify the regulatory DNA element involved in the abnormal CALCA gene induction during sepsis. This study has been supported from NIH Grant DE016511.