Glucose-regulated transcription of the L-type pyruvate kinase (L-PK) gene is mediated through its glucose response element (G1RE/L4 box) composed of two degenerated E-boxes. Upstream stimulatory factor (USF) is a component of the transcriptional glucose response complex built up on
the G1RE. Cooperation of the G1RE with the contiguous binding site (L3 box) for the orphan nuclear receptor hepatocyte nuclear factor 4 (HNF4) has also been suggested. We compared by transient transfection assays the effects of USF2a and other basic helix-loop-helix leucine zipper (bHLH-LZ)
factors (TFE3, c-Myc, SREBP/ADDl) on the activity and glucose responsiveness of a minimal L-PK promoter directed by oligomerized glucose response units (L4L3 boxes). We found that: (i) although USF2a is intrinsically a moderate transcriptional activator, it has a strong stimulatory effect
on the activity of the L4L3-based reporter construct in hepatocyte-derived cells and interferes with the glucose responsiveness; (ii) despite its potent ability as a transactivator, TFE3 alone is barely active on the G1RE in hepatocyte-derived cells; (iii) TFE3 as USF2a acts synergistically
with HNF4 and abolishes glucose responsiveness of the promoter when overexpressed; (iv) in contrast, overexpression of HNF4 alone stimulates activity of the promoter without interfering with glucose responsiveness; (v) SREBP/ADDl has a very weak activity on the L4L3 elements, only detectable
in the presence of HNF4, and c-Myc does not interact with the G1RE of the L-PK promoter. Our studies indicate that different bHLH-LZ transcription factors known to recognize CACGTG-type E-boxes are not equivalent in acting through the L-PK glucose response element, with USF proteins being
especially efficient in hepatocyte-derived cells.
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Basic helix-loop-helix leucine zipper;
L-Type pyruvate kinase;
Upstream stimulatory factor
Document Type: Research Article
Publication date: January 1, 1998
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Gene Expression The Journal of Liver Research will publish articles in all aspects of hepatology. Hepatology, as a research discipline, has seen unprecedented growth especially in the cellular and molecular mechanisms of hepatic health and disease, which continues to have a major impact on understanding liver development, stem cells, carcinogenesis, tissue engineering, injury, repair, regeneration, immunology, metabolism, fibrosis, and transplantation. Continued research and improved understanding in these areas will have a meaningful impact on liver disease prevention, diagnosis, and treatment. The existing journal Gene Expression has expanded its focus to become Gene Expression The Journal of Liver Research to meet this growing demand. In its revised and expanded scope, the journal will publish high-impact original articles, reviews, short but complete articles, and special articles (editorials, commentaries, opinions) on all aspects of hepatology, making it a unique and invaluable resource for readers interested in this field. The expanded team, led by an Editor-in-Chief who is uniquely qualified and a renowned expert, along with a dynamic and functional editorial board, is determined to make this a premier journal in the field of hepatology.
From Volume 16, Gene Expression The Journal of Liver Research is Open Access under the terms of the Creative Commons CC BY-NC-ND license.