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KMID : 0624219980060000040
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Focus on Genetic Science
1998 Volume.6 No. 0 p.40 ~ p.56
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Synergistic Transactivation of the ATP-Citrate Lyase Promoter by SREBP NF-Y
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Moon, Young-Ah
Park, Shang-Wook/Kim, Kyung-Sup
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Abstract
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ATP-citrate lyase (ACL) is a cytosolic enzyme catalyzing the cleavage of citrate and supplying acetyl-CoA for lipogenesis and cholesterogenesis. The ACL-promoter-luciferase gene was drastically stimulated by overexpression of SREBP1a in various cell lines. However, SREBP2 stimulated ACL promoter much less than SREBP1a in Heal and Alexsander cell lines, and did not in CHO and H9C2 cell lines. This result suggests that SREBP1a and 2 have different binding specificities and/or differential usage of the coactivators. A deletion analysis demonstrated that the elements responsive for SREBP are located within 55 base pair sequence between -114 and -60. SREBP1a was able to bind the four region within 55 base pair sequence, of which the novel sequence (-102 to -94) immediate upstream of Y-box and SRE1-consensus sequence (-70 to -61) adjacent to SP1-binding element have functional roles in SREBP-mediated stimulation. The mutation in Y-box and the overexpression of dominant negative NF-Y severely attenuated the transactivation by SREBP, suggesting that NF-y-binding is prerequisite for the action of SREBP. However, SP1-binding element, immediate downstream of SRE1-consensus sequence, plays a minimal role in basal activity and transactivation by SREBP on ACL-promoter. These findings indicate that functional SREs on the promoter of ACL gene allow ACL to be coregulated with other genes involved in lipid metabolism.
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