Computational identification and experimental validation of PPRE motifs in NHE1 and MnSOD genes of Human

Background: Activation of PPARs has been reported to inhibit the proliferation of malignant cells from different lineages. They are involved in transcription regulation of genes upon activation by a ligand. The binding of PPARs to the promoter sequence either represses or activates the gene. Henc...

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Bibliographic Details
Main Authors: Venkatachalam, Gireedhar, Kumar, Alan Prem, Yue, Loo Ser, Pervaiz, Shazib, Clement, Marie Veronique, Sakharkar, Meena Kishore
Other Authors: Singapore-MIT Alliance in Research and Technology (SMART)
Format: Article
Language:en_US
Published: BioMed Central 2011
Online Access:http://hdl.handle.net/1721.1/64781
Description
Summary:Background: Activation of PPARs has been reported to inhibit the proliferation of malignant cells from different lineages. They are involved in transcription regulation of genes upon activation by a ligand. The binding of PPARs to the promoter sequence either represses or activates the gene. Hence, PPARs represent promising targets for cancer treatment because of their anti-proliferative and pro-apoptotic activities. Here we computationally identified PPAR binding regions in NHE1 and MnSOD. We further validated the predictions in vitro. Results: Our results computationally predicted the presence of 2 PPRE motifs in NHE1 and 3 PPRE motifs in MnSOD. We experimentally confirmed the true motifs and their regulation by PPAR. Conclusion: Our results suggest that both NHE1 and MnSOD have PPRE binding motif in their upstream/promoter region and hence are regulated by PPAR upon ligand binding.