Activation of vascular endothelial growth factor A transcription in tumorigenic glioblastoma cell lines by an enhancer with cell type-specific DNase I accessibility.

The Journal of Biological Chemistry
Yuxin LiangCasey C Case

Abstract

Unregulated expression of vascular endothelial growth factor-A (VEGF-A) plays an important role in tumor growth. We have identified a cell type-specific enhancer, HS-1100, that contributes to VEGF-A transcriptional activation in tumorigenic glioblastoma cell lines. This enhancer exhibits increased accessibility to DNase I in glioblastoma cell lines that express high levels of VEGF-A but not in several other cell lines that express much lower levels of VEGF-A. HS-1100 contains a number of sequence elements that are highly conserved among human, mouse, and rat, including the hypoxia-response element (HRE). We show that the HRE contributes significantly to the cell type-specific enhancer activity of HS-1100 in U87MG glioblastoma cells. We use chromatin immunoprecipitation assays to show that endothelial PAS domain protein 1 (EPAS1) can efficiently bind to the endogenous HRE in U87MG cells but not in HEK293 cells in which the chromosomal HS-1100 is not accessible to DNase I. A dominant negative EPAS1 significantly reduces HS-1100 enhancer activity and VEGF-A levels in U87MG cells. Our results provide insight into the molecular mechanisms of VEGF-A up-regulation during cancer development.

References

Jul 1, 1977·Journal of the National Cancer Institute·J FoghT Orfeo
Nov 1, 1973·Journal of the National Cancer Institute·D J GiardW P Parks
Nov 1, 1995·Glia·K H Plate, W Risau
Aug 6, 1996·Proceedings of the National Academy of Sciences of the United States of America·S Y ChengW K Cavenee
Sep 1, 1996·Molecular and Cellular Biology·J A ForsytheG L Semenza
Nov 5, 1997·The Journal of Biological Chemistry·C L Smith, G L Hager
Mar 17, 1999·International Journal of Cancer. Journal International Du Cancer·M M FeldkampA Guha
Nov 26, 1999·International Journal of Developmental Neuroscience : the Official Journal of the International Society for Developmental Neuroscience·M M ValterT Pietsch
Sep 20, 2000·Proceedings of the National Academy of Sciences of the United States of America·M D MuellerR N Taylor
Sep 23, 2000·Nature·P Carmeliet, R K Jain
Dec 5, 2000·Current Opinion in Biotechnology·N Ferrara
May 30, 2001·Current Opinion in Genetics & Development·P H MaxwellP J Ratcliffe

❮ Previous
Next ❯

Citations

Jan 15, 2014·Archives of Biochemistry and Biophysics·Hui-Jung JungWon-Ki Baek
Mar 6, 2003·Mechanisms of Ageing and Development·Casey C Case
Jan 22, 2010·The Journal of Biological Chemistry·Jian Fu, Mark B Taubman
Sep 30, 2003·Proceedings of the National Academy of Sciences of the United States of America·Siyuan TanPhilip D Gregory
Oct 20, 2009·Biochemical and Biophysical Research Communications·Tomoaki MoriTakashi Sera
Feb 4, 2006·Magnetic Resonance Imaging·Donglai HuoDavid Wilson
Apr 22, 2008·Biochemical and Biophysical Research Communications·Shiro KoizumeYohei Miyagi
Sep 22, 2016·Clinical Epigenetics·Inês GraçaCarmen Jerónimo
Mar 10, 2004·Journal of Biomolecular Screening·Pei-Qi LiuNigel P Shankley
Dec 10, 2015·Nanoscale·Lasse EvensenGareth Griffiths
Dec 16, 2006·Biotechnology and Bioengineering·Andreas ReikPhilip D Gregory
Apr 11, 2019·Oncogene·Maria Patrizia MongiardiMaria Laura Falchetti

❮ Previous
Next ❯

Related Concepts

Related Feeds

ASBMB Publications

The American Society for Biochemistry and Molecular Biology (ASBMB) includes the Journal of Biological Chemistry, Molecular & Cellular Proteomics, and the Journal of Lipid Research. Discover the latest research from ASBMB here.

CREs: Gene & Cell Therapy

Gene and cell therapy advances have shown promising outcomes for several diseases. The role of cis-regulatory elements (CREs) is crucial in the design of gene therapy vectors. Here is the latest research on CREs in gene and cell therapy.