Characterization of a kidney-specific pattern of chromatin structure in the rat phosphoenolpyruvate carboxykinase gene

The kidney-specific chromatin structure of the phosphoenolpyruvate carboxyk inase (PEPCK) gene was examined and compared to that of the liver. Kidney n uclear extracts were found to lack a liver-enriched factor, pepA, that bind s to HSS A, a distal enhancer of the PEPCK gene that may be involved in ope ning the chromatin domain of the PEPCK gene in the liver. To begin the char acterization of the kidney-specific chromatin structure of the PEPCK gene, nuclease hypersensitive sites (HSS) were mapped by indirect end-labeling an alysis in proximal tubules from control rats, proximal tubules from acidoti c rats which express induced levels of PEPCK, and NRK52E cells, a rat kidne y epithelial cell line which does not express the PEPCK gene. A subset of H SS, at -400/+1 over the proximal promoter and at +1900 within the coding re gion, correlate with kidney-specific PEPCK expression Two other HSS, at -3. 1 kb and +6.2 kb, are detected in kidney cells regardless of PEPCK expressi on. The HSS at -4800, -1240, and +4650, previously identified in PEPCK-expr essing liver cells, were not observed in the kidney. As in the liver, the p attern of hypersensitivity in the kidney does not change by altering the ra te of transcription. (C) 1999 Elsevier Science B.V. All rights reserved.