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Fibronectin transcription in liver cells: promoter occupation and function in sinusoidal endothelial cells and hepatocytes

journal contribution
posted on 2023-06-07, 21:29 authored by Claudio AlonsoClaudio Alonso, Jacob George, C Gustavo Pesce, D Montgomery Bissell, Alberto R Kornblihtt
Hepatocytes (Heps) and sinusoidal endothelial cells (SECs) perform different roles in normal and pathological liver functions through the differential expression of fibronectin (FN) polypeptides. Nonetheless, the molecular basis underlying cell-type specific FN expression remains unknown. Using liver cell isolation techniques followed by short-term primary culture and transient transfection, here, we compare the transcriptional regulation of the FN promoter in Heps and SEC in conditions that closely resemble in vivo physiology. Transfection experiments allowed us to reveal cell-type specific regulatory elements operating through the proximal regions of the FN promoter. To investigate this further, we examined the occupation patterns of key elements of the FN promoter such as the -170 CRE and -150 CCAAT sites. Transcriptional activity of mutagenised promoter constructs confirmed that in Heps, these two sites behave as a composite element critical for normal promoter activity. In addition, DNA-binding experiments demonstrate that the -170 CRE element displays a clear cell-type specific occupation with binding activities for ATF-2 and ATF-3 being specific to Heps. These results establish the starting point to investigate the molecular basis of changes in transcriptional regulation of the FN gene involved in liver pathology. 2002 Elsevier Science (USA). All rights reserved.

History

Publication status

  • Published

Journal

Biochemical and Biophysical Research Communications

ISSN

0006-291X

Issue

5

Volume

295

Page range

1077-1084

Department affiliated with

  • Evolution, Behaviour and Environment Publications

Full text available

  • No

Peer reviewed?

  • Yes

Legacy Posted Date

2012-02-06

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