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Genome-wide Orchestration of Cardiac Functions by the Orphan Nuclear Receptors ERRα and γ.
- Source :
- Cell Metabolism; May2007, Vol. 5 Issue 5, p345-356, 12p
- Publication Year :
- 2007
-
Abstract
- Summary: Orphan nuclear receptor ERRα (NR3B1) is recognized as a key regulator of mitochondrial biogenesis, but it is not known whether ERRα 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 ERRα and γ (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<superscript>2+</superscript> 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. [Copyright &y& Elsevier]
- Subjects :
- MUSIC orchestration
CARDIOMYOPATHIES
IMMUNOSPECIFICITY
CELL membranes
Subjects
Details
- Language :
- English
- ISSN :
- 15504131
- Volume :
- 5
- Issue :
- 5
- Database :
- Supplemental Index
- Journal :
- Cell Metabolism
- Publication Type :
- Academic Journal
- Accession number :
- 24972613
- Full Text :
- https://doi.org/10.1016/j.cmet.2007.03.007