Table 1.
ERRα target genes in metabolism
Metabolic pathway |
Gene | Regulated by ERRα in | Direct target in | Promoter study? |
---|---|---|---|---|
Fatty acid oxidation |
Acadm (Mcad) | HeLa [24], SAOS2 [26], C2C12 [29], MDA-MB-231 [15], HL-1 atrial myocytes [49], soleus muscle [42], BAT [44], heart [52] |
BAT [44], heart [49] | Yes [23] |
Cpt1b | MEFs [45], BAT [44] | BAT [44] | – | |
TCA cycle | Aco2 | Macrophages [46]; BAT [44] | BAT [44], macrophages [46] | – |
Idh3a | SAOS2 [26], HepG2 [41,56], macrophages [46]; BAT [44] | BAT [44], macrophages [46] | – | |
Sdha | Macrophages [46] | Macrophages [46] | – | |
Sdhd | Macrophages [46] | Heart [49], macrophages [46] | – | |
OxPhos | Atp5b | SAOS2 [26], HepG2 [41,56], macrophages [46]; liver [56], BAT [44] |
BAT [44], heart [49], macrophages [46] | Yes [26] |
Atp5 g3 | Macrophages [46] | Macrophages [46] | – | |
Coq7 | Macrophages [46] | Macrophages [46] | – | |
Cox8a | Macrophages [46] | Macrophages [46] | – | |
Cycs | SAOS2 [26], HepG2 [41,56], MEFs [45], macrophages [46]; BAT [44], heart [52] |
BAT [44], heart [49], macrophages [46] | Yes [26,49] | |
Ndufs7 | Macrophages [46] | Macrophages [46] | – | |
Mitochondrial transport |
Timm13a | Macrophages [46] | Macrophages [46] | – |
Slc25a4 (Ant1) | HepG2 [41], heart [52] | Heart [49], macrophages [46] | – | |
Mitochondrial dynamics |
Mfn2 | SAOS2 [35] | SAOS2 [35], HeLa [47] | Yes [47] |
Regulator of metabolism |
Esrra | C2C12 [29], MDA-MB-231 [15], | Heart [49] | Yes [28,29] |
Ppara | HepG2 [41], BAT [44], heart [52] | L6 myoblasts [42] | Yes [42] | |
Gabpa (Nrf2A) | C2C12 [29], FAO hepatoma [29], MEFs [45] | Heart [49], macrophages [46] | Yes [29] | |
Nrip1 (Rip140) | 3T3-L1 [66] | 3T3-L1 [66] | Yes [66] | |
Lipid transport | Apoa4 | Intestine [43] | Caco-2 [43] | Yes [43] |
Gluco/Glycero- neogenesis |
Pck1 (Pepck)* | H4IIE hepatoma cells [56]; liver [56] | H4IIE [56] | Yes [34,56] |
ERRα targets shown here are ones with roles in metabolism, regulated by endogenous ERRα (i.e. genes whose expression is reduced, as determined by quantitative RT–PCR, in cells when ERRα is inhibited by siRNA or the inverse agonist XCT790, cells derived from ERRα null mice, or tissues of ERRα null mice) and directly recognized by ERRα (i.e. direct ERRα targets, as determined by quantitative ChIP). Target genes whose ERRE-containing regulatory regions have been tested for conferring ERRα/PGC-1 regulation to reporter genes in transient transfections are indicated by ‘yes’ under ‘promoter study’. Notably, some targets are regulated by ERRα in a cell-type specific manner. For example, Acadm is not regulated by ERRα in macrophages [46] and Gabpa is not regulated by ERRα in SAOS2 [26] and macrophages [46].
Pepck is repressed by ERRα (all other targets shown here are activated by ERRα).