| First Author | Pan H | Year | 2014 |
| Journal | Cell Rep | Volume | 7 |
| Issue | 1 | Pages | 79-85 |
| PubMed ID | 24656816 | Mgi Jnum | J:211827 |
| Mgi Id | MGI:5576446 | Doi | 10.1016/j.celrep.2014.02.028 |
| Citation | Pan H, et al. (2014) Negative elongation factor controls energy homeostasis in cardiomyocytes. Cell Rep 7(1):79-85 |
| abstractText | Negative elongation factor (NELF) is known to enforce promoter-proximal pausing of RNA polymerase II (Pol II), a pervasive phenomenon observed across multicellular genomes. However, the physiological impact of NELF on tissue homeostasis remains unclear. Here, we show that whole-body conditional deletion of the B subunit of NELF (NELF-B) in adult mice results in cardiomyopathy and impaired response to cardiac stress. Tissue-specific knockout of NELF-B confirms its cell-autonomous function in cardiomyocytes. NELF directly supports transcription of those genes encoding rate-limiting enzymes in fatty acid oxidation (FAO) and the tricarboxylic acid (TCA) cycle. NELF also shares extensively transcriptional target genes with peroxisome proliferator-activated receptor alpha (PPARalpha), a master regulator of energy metabolism in the myocardium. Mechanistically, NELF helps stabilize the transcription initiation complex at the metabolism-related genes. Our findings strongly indicate that NELF is part of the PPARalpha-mediated transcription regulatory network that maintains metabolic homeostasis in cardiomyocytes. |
