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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 and Christopher A. Bradfield
Proceedings of the National Academy of Sciences of the United States of America
Vol. 95, No. 10 (May 12, 1998), pp. 5474-5479
Stable URL: http://www.jstor.org/stable/45109
Page Count: 6
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The Basic-Helix-Loop-Helix-PAS Orphan MOP3 Forms Transcriptionally Active Complexes with Circadian and Hypoxia Factors
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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 1α (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.

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