Title

Negative elongation factor controls energy homeostasis in cardiomyocytes

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.

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