H. Fukuda et al., INSULIN-RESPONSIVE AND POLYUNSATURATED FATTY ACID-RESPONSIVE REGION(S) OF RAT ATP CITRATE-LYASE GENE PROMOTER, FEBS letters, 380(1-2), 1996, pp. 204-207
To investigate the regulatory DNA sequences required for insulin-stimu
lation of the ATP citrate-lyase (ACL) gene as well as for polyunsatura
ted fatty acid (PUFA)-suppression of this gene, primary cultured hepat
ocytes were transfected with plasmids containing the 5'-flanking seque
nce of the rat ACL gene fused to the chloramphenicol acetyltransferase
(CAT) gene, Sequences from -861, -194 or -104 to +128 of the ACL gene
directed an increase in CAT activity in hepatocytes when insulin was
added to the medium containing either glucose or pyruvate, The CAT act
ivities stimulated by insulin were reduced by the addition of PUFA, in
accordance with the responses on the endogenous ACL gene expression,
Further deletion to -20, however, resulted in loss of the responses. T
he results suggest that the region from -104 to -20 of the ACL gene is
responsible for regulation due to insulin and PUFAs. In particular, t
he region from -61 to -49 of the ACL has sequence similarity to the in
sulin-responsive regions of fatty acid synthase and acetyl-CoA carboxy
lase.