[Ap1-like cis-elements in 5'-regulatory region of human apolipoprotein A-I gene].
Several Ap1-like cis-acting elements were found within 5'-regulatory region (-2497...+173 versus transcription start point) of human apolipoprotein A-I gene (5'-apoA-I). Those elements are capable to interact with transcription factors belonging to Ap1 and CREB/ATF families. Those elements are localized outside of the hepatic enhancer (-220...-110) and the sequence responsible for apoA-I gene transcription in Caco2 cells (-595...-192). One of Ap1-like sites (5'-TGAGGTCT-3, Cre/jun2/apo) is present within 5'-apoA-I in two copies - distal (-1798 ...-1791) and proximal (+99...+106) ones. This and other Ap1-like sites - 5'-TGACTCT-3' (-1798...-1791, PF1) and 5'-TGACATCA-3' (-1171...-1163, Cre/jun1) were characterized by EMSA. It was shown by using the specific antibodies to c-Jun and ATF2 transcription factors in EMSA supershift experiments, that the DNA-protein complexes formed by Cre/jun2/apo, Cre/jun1 elements with nuclear proteins of human hepatoma HepG2 cells contain ATF2. The functional role of 5'-apoA-I regions containing Ap1-like sites was studied in cotransfection experiments of HepG2 cells (synthesize endogenous ApoA-I), human duodenum adenocarcinoma Hutu80 cells (do not synthesize endogenous ApoA-I), human neuroblastoma SK-N-SH cells (do not synthesize endogenous A-I) with expression vectors of c-jun and mekk1 genes. It was shown, that those Ap1-like sites appears to be responsible (the proximal Cre/jun2/apo is more efficient) for tissue-specific regulation of human apoA-I gene expression.
Lapikov
I A
IA
Mogilenko
D A
DA
Dizhe
E B
EB
Ignatovich
I A
IA
Orlov
S V
SV
Perevozchikov
A P
AP
D051698:Activating Transcription Factor 2 / Q000235:genetics / Q000378:metabolism*; D016632:Apolipoprotein A-I / Q000096:biosynthesis* / Q000235:genetics; D018938:Caco-2 Cells; D005786:Gene Expression Regulation / Q000502:physiology*; D006801:Humans; D009928:Organ Specificity; D016755:Proto-Oncogene Proteins c-jun / Q000235:genetics / Q000378:metabolism*; D020218:Response Elements / Q000502:physiology*; D018808:Transcription Factor AP-1 / Q000235:genetics / Q000378:metabolism*
C497105:ATF2 protein, human; D051698:Activating Transcription Factor 2; D016632:Apolipoprotein A-I; D016755:Proto-Oncogene Proteins c-jun; D018808:Transcription Factor AP-1