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

• Published in: Molecular biology (New York) Vol. 42; no. 2; pp. 261 - 269
• Main Authors: Lapikov, I. A., Mogilenko, D. A., Dizhe, E. B., Ignatovich, I. A., Orlov, S. V., Perevozchikov, A. P.
• Format: Journal Article
• Language: English
• Published: Dordrecht SP MAIK Nauka/Interperiodica 01-04-2008; Springer Nature B.V
• Subjects: Apolipoproteins; Biochemistry; Biomedical and Life Sciences; Cell Molecular Biology; Gene expression; Human Genetics; Kinases; Life Sciences; Molecular biology; Proteins; Hutu80 duodenal carcinoma cell line; ATF2; Mekk1 protein kinase; Ap1-like; Ap1; SK-N-SH neuroblastoma cell line; transcription factors; elements; 5′-regulatory region of the human apolipoprotein A-I gene; human cell lines; HepG2 hepatoma cell line
• ISSN: 0026-8933; 1608-3245
• DOI: 10.1134/S002689330802012X

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.