Ap1-like cis elements in the 5′-regulatory region of the human apolipoprotein A-I gene

I. A. Lapikov, D. A. Mogilenko, E. B. Dizhe, I. A. Ignatovich, S. V. Orlov, A. P. Perevozchikov

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3 Scopus citations

Abstract

Ap1-like cis elements, interacting with transcription factors of the Ap1 and CREB/ATF families, were identified in the 5′-regulatory region of the human apolipoprotein A-I gene (5′-apoA-I). The elements are beyond the hepatic enhancer (-220...-110) and region -595...-192, responsible for efficient transcription in Caco2 cells. One of the elements (5′-TGAGGTCT-3′, Cre/jun2/apo) occurs in 5′-apoA-I in two copies, distal (-2176...-2165) and proximal (99...106). The electrophoretic mobility shift assay was used to characterize this and two other 5′-apoA-I Ap1-like elements: 5′-TGACTCT-3′ (-1798...-1791, PF1) and 5′-TGACATCA-3′ (-1171...-1163, Cre/jun1). Experiments with specific antibodies identified ATF2 as a component of the complexes formed by HepG2 nuclear proteins with Cre/jun2/apo and Cre/jun1. Several 5′-apoA-I deletion derivatives were examined in HepG2 hepatoma cells (producing ApoA-I), Hutu80 duodenal adenocarcinoma cells (lacking ApoA-I production), and SK-N-SH neuroblastoma cells (carrying defective apoA-I) by the luciferase reporter assay. Combined with cell cotransfection with c-jun and mekk1 expression vectors, the assays implicated the Ap1-like elements in the tissue-specific regulation of apoA-I expression, the proximal Cre/jun2/apo element playing the major role.

Original languageEnglish
Pages (from-to)261-269
Number of pages9
JournalMolecular Biology
Volume42
Issue number2
DOIs
StatePublished - Apr 2008

Keywords

  • 5′-regulatory region of the human apolipoprotein A-I gene
  • ATF2
  • Ap1
  • Ap1-like cis elements
  • HepG2 hepatoma cell line
  • Human cell lines
  • Hutu80 duodenal carcinoma cell line
  • Mekk1 protein kinase
  • SK-N-SH neuroblastoma cell line
  • Transcription factors

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