title: Negative elongation factor controls energy homeostasis in cardiomyocytes.
abstract: 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 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.
authors.affiliation: Department of Molecular Medicine, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA.
authors.forename: Haihui
authors.initials: H
authors.lastname: Pan
authors.affiliation: Department of Molecular Medicine, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA.
authors.forename: Kunhua
authors.initials: K
authors.lastname: Qin
authors.affiliation: Greehey Children's Cancer Research Institute, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA; Department of Epidemiology and Biostatistics, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA.
authors.forename: Zhanyong
authors.initials: Z
authors.lastname: Guo
authors.affiliation: Department of Medicine, San Antonio Cardiovascular Proteomics Center, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA.
authors.forename: Yonggang
authors.initials: Y
authors.lastname: Ma
authors.affiliation: Illumina, Inc., San Diego, CA 92121, USA.
authors.forename: Craig
authors.initials: C
authors.lastname: April
authors.affiliation: Department of Biochemistry, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA.
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Gao
authors.affiliation: Greehey Children's Cancer Research Institute, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA.
authors.forename: Thomas G
authors.initials: TG
authors.lastname: Andrews
authors.affiliation: Department of Epidemiology and Biostatistics, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA.
authors.forename: Alex
authors.initials: A
authors.lastname: Bokov
authors.affiliation: Department of Medicine, San Antonio Cardiovascular Proteomics Center, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA.
authors.forename: Jianhua
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Greehey Children's Cancer Research Institute, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA; Department of Epidemiology and Biostatistics, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA.
authors.forename: Yidong
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Biochemistry, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA.
authors.forename: Susan T
authors.initials: ST
authors.lastname: Weintraub
authors.affiliation: Illumina, Inc., San Diego, CA 92121, USA.
authors.forename: Jian-Bing
authors.initials: JB
authors.lastname: Fan
authors.affiliation: Greehey Children's Cancer Research Institute, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA; Department of Epidemiology and Biostatistics, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA.
authors.forename: Degeng
authors.initials: D
authors.lastname: Wang
authors.affiliation: Department of Molecular Medicine, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA.
authors.forename: Yanfen
authors.initials: Y
authors.lastname: Hu
authors.affiliation: Greehey Children's Cancer Research Institute, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA; Department of Pediatrics, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA.
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Aune
authors.affiliation: Department of Medicine, San Antonio Cardiovascular Proteomics Center, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA. Electronic address: mllindsey@umc.edu.
authors.forename: Merry L
authors.initials: ML
authors.lastname: Lindsey
authors.affiliation: Department of Molecular Medicine, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA. Electronic address: lir3@uthscsa.edu.
authors.forename: Rong
authors.initials: R
authors.lastname: Li
mesh_terms: D000818:Animals; D009202:Cardiomyopathies / Q000235:genetics / Q000378:metabolism; D004452:Echocardiography; D004734:Energy Metabolism / Q000235:genetics; D006706:Homeostasis; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D032383:Myocytes, Cardiac / Q000166:cytology / Q000378:metabolism*; D047493:PPAR alpha / Q000235:genetics / Q000378:metabolism; D012319:RNA Polymerase II / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic
chemical_list: C582413:NELF protein, mouse; D047493:PPAR alpha; D014157:Transcription Factors; D012319:RNA Polymerase II