+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

Transcriptional regulation of the nuclear gene encoding the alpha-subunit of the mammalian mitochondrial F1F0 ATP synthase complex: role for the orphan nuclear receptor, COUP-TFII/ARP-1



Transcriptional regulation of the nuclear gene encoding the alpha-subunit of the mammalian mitochondrial F1F0 ATP synthase complex: role for the orphan nuclear receptor, COUP-TFII/ARP-1



Biochemistry 42(9): 2656-2663



Our laboratory has been studying the transcriptional regulation of the nuclear gene (ATPA) that encodes the alpha-subunit of the mammalian mitochondrial F1F0 ATP synthase complex. We have previously determined that the regulatory factor, upstream stimulatory factor 2 (USF2), can stimulate transcription of the ATPA gene through the cis-acting regulatory element 1 in the upstream promoter of this gene. In this study, we used the yeast one-hybrid screening method to identify another factor, COUP-TFII/ARP-1, which also binds to the ATPA cis-acting regulatory element 1. Binding of the orphan nuclear receptor, COUP-TFII/ARP-1, to the ATPA regulatory element 1 was confirmed using electrophoretic mobility shift experiments, and COUP-TFII/ARP-1-containing complexes were detected in HeLa cell nuclear extracts. A mutational analysis indicated that the binding site for COUP-TFII/ARP-1 in the ATPA regulatory element 1 is an imperfect direct repeat of a nuclear receptor response element (A/GGGTCA) with a spacer of three nucleotides. Functional assays in HeLa cells showed that COUP-TFII/ARP-1 represses the ATPA promoter activity in a dose- and sequence-dependent manner. Furthermore, cotransfection assays demonstrated that COUP-TFII/ARP-1 inhibits the USF2-mediated activation of the wild-type ATPA gene promoter but not a mutant promoter that is defective in COUP-TFII/ARP-1-binding. Overexpression of USF2 reversed the COUP-TFII/ARP-1-mediated repression of the ATPA promoter. Mobility shift assays revealed that COUP-TFII/ARP-1 and USF2 compete for binding to the ATPA regulatory element 1. Thus, the ATPA gene is regulated by a multifunctional binding site through which the transcription factors, COUP-TFII/ARP-1 and USF2, bind and exert their antagonistic effects.

Please choose payment method:






(PDF emailed within 0-6 h: $19.90)

Accession: 060415178

Download citation: RISBibTeXText

PMID: 12614160

DOI: 10.1021/bi0268347


Related references

Transcriptional regulation of the nuclear gene encoding the alpha-subunit of the mammalian mitochondrial F1F0 ATP synthase complex Role for the orphan nuclear receptor, COUP-TFII/ARP-1. Molecular Biology of the Cell 13(Suppl.): 101a, 2002

Transcriptional Regulation of the Nuclear Gene Encoding the a-Subunit of the Mammalian Mitochondrial F1F0 ATP Synthase Complex: Role for the Orphan Nuclear Receptor, COUP-TFII/ARP-1. Biochemistry (American Chemical Society) 42(9): 56-63, 2003

The orphan nuclear receptors COUP-TFI and COUP-TFII regulate expression of the gonadotropin LHβ gene. Molecular and Cellular Endocrinology 330(1-2): 59-71, 2010

The INSL3 gene is a direct target for the orphan nuclear receptor, COUP-TFII, in Leydig cells. Journal of Molecular Endocrinology 53(1): 43-55, 2014

Regulation of the nuclear gene that encodes the alpha-subunit of the mitochondrial ATP synthase complex. Molecular Biology of the Cell 7(Suppl. ): 631A, 1996

The nuclear orphan receptor COUP-TFII plays an essential role in adipogenesis, glucose homeostasis, and energy metabolism. Cell Metabolism 9(1): 77-87, 2009

Involvement of orphan nuclear receptor COUP-TFII in cadherin-6 and cadherin-11 regulation: implications in development and cancer. Mechanisms of Development 136: 64-72, 2015

Transcriptional regulation of human Rev-erbalpha gene expression by the orphan nuclear receptor retinoic acid-related orphan receptor alpha. Journal of Biological Chemistry 277(51): 49275-49281, 2002

Inactivation of the Nuclear Orphan Receptor COUP-TFII by Small Chemicals. Acs Chemical Biology 12(3): 654-663, 2017

The orphan nuclear receptor COUP-TFII is required for angiogenesis and heart development. Genes & Development 13(8): 1037-1049, 1999

The orphan nuclear receptor, COUP-TF II, inhibits myogenesis by post-transcriptional regulation of MyoD function: COUP-TF II directly interacts with p300 and myoD. Nucleic Acids Research 26(23): 5501-5510, 1998

Regulation of the nuclear gene that encodes the alpha-subunit of the mitochondrial F0F1-ATP synthase complex. Activation by upstream stimulatory factor 2. Journal of Biological Chemistry 272(16): 10538-10542, 1997

Identification of COUP-TFII orphan nuclear receptor as a retinoic acid-activated receptor. Plos Biology 6(9): E227, 2008

Deletion of the orphan nuclear receptor COUP-TFII in uterus leads to placental deficiency. Proceedings of the National Academy of Sciences of the United States of America 104(15): 6293-6298, 2007

The nuclear orphan receptor COUP-TFII is required for limb and skeletal muscle development. Molecular and Cellular Biology 24(24): 10835-10843, 2004