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Arch Biochem Biophys. 2002 Jan 15;397(2):258-61.

CAAT/enhancer binding protein activates an enhancer in the glutamine synthetase distal 5'-flanking sequence.

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  • 1Research Service, The John D. Dingell VA Medical Center, 4646 John R., Detroit, Michigan 48201, USA.


The glutamine synthetase (GS) gene is expressed at high levels in several cell types, including astrocytes, pericentral hepatocytes, and adipocytes. During hormone-mediated adipocyte differentiation of 3T3-L1 cells, GS gene expression increases several hundred fold. We previously reported that elements in the distal 5'-flanking sequence and intron-1 participate in establishing the temporal pattern of GS transcription during adipocyte differentiation. To examine the role of the distal 5'-flanking region in regulating adipocyte-specific GS expression, GS-CAT fusion genes were constructed and analyzed in transiently transfected 3T3-L1 cells. In this way, adipocyte differentiation-responsive enhancer activity was localized to a 422-bp sequence that occurs about 3.5 kb upstream from the transcription start site. This sequence includes several putative C/EBP binding sites and is activated by ectopic expression of C/EBPalpha in NIH-3T3 cells. Thus, our data indicate that C/EBPalpha has the capacity to activate functional C/EBP sites in the GS gene distal 5'-flanking region.

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