Negative elongation factor controls energy homeostasis in cardiomyocytes

Authors

Haihui Pan, University of Texas Health Science Center at San Antonio
Kunhua Qin, University of Texas Health Science Center at San Antonio
Zhanyong Guo, University of Texas Health Science Center at San Antonio
Yonggang Ma, University of Texas Health Science Center at San Antonio
Craig April, Illumina, Inc.
Xiaoli Gao, University of Texas Health Science Center at San Antonio
Thomas G. Andrews, University of Texas Health Science Center at San Antonio
Alex Bokov, University of Texas Health Science Center at San Antonio
Jianhua Zhang, University of Texas Health Science Center at San Antonio
Yidong Chen, University of Texas Health Science Center at San Antonio
Susan T. Weintraub, University of Texas Health Science Center at San Antonio
Jian Bing Fan, Illumina, Inc.
Degeng Wang, University of Texas Health Science Center at San Antonio
Yanfen Hu, University of Texas Health Science Center at San Antonio
Gregory J. Aune, University of Texas Health Science Center at San Antonio
Merry L. Lindsey, University of Texas Health Science Center at San Antonio
Rong Li, University of Texas Health Science Center at San Antonio

Document Type

Journal Article

Publication Date

10-4-2014

Journal

Cell Reports

Volume

7

Issue

1

DOI

10.1016/j.celrep.2014.02.028

Abstract

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.

APA Citation

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