The basic-helix-loop-helix-PAS orphan MOP3 forms transcriptionally active complexes with circadian and hypoxia factors

John B. Hogenesch, Yi Zhong Gu, Sanjay Jain, Christopher A. Bradfield

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609 Scopus citations

Abstract

We report that MOP3 is a general dimerization partner for a subset of the basic-helix-loop-helix (bHLH)-PER-ARNT-SIM (PAS) superfamily of transcriptional regulators. We demonstrated that MOP3 interacts with MOP4, CLOCK, hypoxia-inducible factor la (HIF1α), and HIF2α. A DNA selection protocol revealed that the MOP3-MOP4 heterodimer bound a CACGTGA-containing DNA element. Transient transfection experiments demonstrated that the MOP3- MOP4 and MOP3-CLOCK complexes bound this element in COS-1 cells and drove transcription from a linked luciferase reporter gene. We also deduced the high-affinity DNA binding sites for MOP3-HIF1α complex (TACGTGA) and used transient transfection experiments to demonstrate that the MOP3-HIF1α and MOP3-HIF2α heterodimers bound this element, drove transcription, and responded to cellular hypoxia. Finally, we found that MOP3 mRNA expression overlaps in a number of tissues with each of its four potential partner molecules in vivo.

Original languageEnglish
Pages (from-to)5474-5479
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume95
Issue number10
DOIs
StatePublished - May 12 1998

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