TY - JOUR
T1 - The basic-helix-loop-helix-PAS orphan MOP3 forms transcriptionally active complexes with circadian and hypoxia factors
AU - Hogenesch, John B.
AU - Gu, Yi Zhong
AU - Jain, Sanjay
AU - Bradfield, Christopher A.
PY - 1998/5/12
Y1 - 1998/5/12
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=0032510778&partnerID=8YFLogxK
U2 - 10.1073/pnas.95.10.5474
DO - 10.1073/pnas.95.10.5474
M3 - Article
C2 - 9576906
AN - SCOPUS:0032510778
SN - 0027-8424
VL - 95
SP - 5474
EP - 5479
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 10
ER -