Genome-wide orchestration of cardiac functions by the orphan nuclear receptors ERRalpha and gamma
- PMID: 17488637
- DOI: 10.1016/j.cmet.2007.03.007
Genome-wide orchestration of cardiac functions by the orphan nuclear receptors ERRalpha and gamma
Abstract
Orphan nuclear receptor ERRalpha (NR3B1) is recognized as a key regulator of mitochondrial biogenesis, but it is not known whether ERRalpha and other ERR isoforms play a broader role in cardiac energetics and function. We used genome-wide location analysis and expression profiling to appraise the role of ERRalpha and gamma (NR3B3) in the adult heart. Our data indicate that the two receptors, acting as nonobligatory heterodimers, target a common set of promoters involved in the uptake of energy substrates, production and transport of ATP across the mitochondrial membranes, and intracellular fuel sensing, as well as Ca(2+) handling and contractile work. Motif-finding algorithms assisted by functional studies indicated that ERR target promoters are enriched for NRF-1, CREB, and STAT3 binding sites. Our study thus reveals that the ERRs orchestrate a comprehensive cardiac transcriptional program and further suggests that modulation of ERR activities could be used to manage cardiomyopathies.
Similar articles
-
Estrogen related receptors (ERRs): a new dawn in transcriptional control of mitochondrial gene networks.Mitochondrion. 2011 Jul;11(4):544-52. doi: 10.1016/j.mito.2011.03.121. Epub 2011 Apr 7. Mitochondrion. 2011. PMID: 21497207 Review.
-
Target specificities of estrogen receptor-related receptors: analysis of binding sequences and identification of Rb1-inducible coiled-coil 1 (Rb1cc1) as a target gene.J Biochem. 2008 Mar;143(3):395-406. doi: 10.1093/jb/mvm231. Epub 2007 Nov 26. J Biochem. 2008. PMID: 18039682
-
Epidermal growth factor-induced signaling in breast cancer cells results in selective target gene activation by orphan nuclear receptor estrogen-related receptor alpha.Cancer Res. 2005 Jul 15;65(14):6120-9. doi: 10.1158/0008-5472.CAN-05-0922. Cancer Res. 2005. PMID: 16024613
-
Estrogen receptor-related receptors: orphan receptors desperately seeking a ligand.J Mol Endocrinol. 2003 Dec;31(3):349-57. doi: 10.1677/jme.0.0310349. J Mol Endocrinol. 2003. PMID: 14664699 Review.
-
Deoxyribonucleic acid response element-dependent regulation of transcription by orphan nuclear receptor estrogen receptor-related receptor gamma.Mol Endocrinol. 2004 Feb;18(2):312-25. doi: 10.1210/me.2003-0165. Epub 2003 Nov 26. Mol Endocrinol. 2004. PMID: 14645497
Cited by
-
Dynamic interplay of nuclear receptors in tumor cell plasticity and drug resistance: Shifting gears in malignant transformations and applications in cancer therapeutics.Cancer Metastasis Rev. 2024 Mar;43(1):321-362. doi: 10.1007/s10555-024-10171-0. Epub 2024 Mar 22. Cancer Metastasis Rev. 2024. PMID: 38517618 Review.
-
The potential of therapeutic strategies targeting mitochondrial biogenesis for the treatment of insulin resistance and type 2 diabetes mellitus.Arch Pharm Res. 2024 Mar;47(3):219-248. doi: 10.1007/s12272-024-01490-5. Epub 2024 Mar 14. Arch Pharm Res. 2024. PMID: 38485900 Review.
-
Pathological mutations reveal the key role of the cytosolic iRhom2 N-terminus for phosphorylation-independent 14-3-3 interaction and ADAM17 binding, stability, and activity.Cell Mol Life Sci. 2024 Feb 27;81(1):102. doi: 10.1007/s00018-024-05132-3. Cell Mol Life Sci. 2024. PMID: 38409522 Free PMC article.
-
COX6C expression driven by copy amplification of 8q22.2 regulates cell proliferation via mediation of mitosis by ROS-AMPK signaling in lung adenocarcinoma.Cell Death Dis. 2024 Jan 19;15(1):74. doi: 10.1038/s41419-024-06443-w. Cell Death Dis. 2024. PMID: 38242874 Free PMC article.
-
Sex differences in mitochondrial gene expression during viral myocarditis.Res Sq [Preprint]. 2023 Dec 19:rs.3.rs-3716881. doi: 10.21203/rs.3.rs-3716881/v1. Res Sq. 2023. PMID: 38196574 Free PMC article. Preprint.
Publication types
MeSH terms
Substances
Associated data
- Actions
Grants and funding
LinkOut - more resources
Full Text Sources
Other Literature Sources
Molecular Biology Databases
Miscellaneous