Negative elongation factor controls energy homeostasis in cardiomyocytes
Negative elongation factor (NELF) is known to enforce promoter-proximal pausing of RNA polymerase II (PolII), 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) inadult 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 α (PPARα), 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 PPARα-mediated transcription regulatory network that maintains metabolic homeostasis in cardiomyocytes. © 2014 The Authors.
Pan, H., Qin, K., Guo, Z., Ma, Y., April, C., Gao, X., Andrews, T., Bokov, A., Zhang, J., Chen, Y., Weintraub, S., Fan, J., Wang, D., Hu, Y., Aune, G., Lindsey, M., & Li, R. (2014). Negative elongation factor controls energy homeostasis in cardiomyocytes. Cell Reports, 7 (1). http://dx.doi.org/10.1016/j.celrep.2014.02.028