title: KLF15 Establishes the Landscape of Diurnal Expression in the Heart.
abstract: Circadian rhythms offer temporal control of anticipatory physiologic adaptations in animals. In the mammalian cardiovascular system, the importance of these rhythms is underscored by increased cardiovascular disease in shift workers, findings recapitulated in experimental animal models. However, a nodal regulator that allows integration of central and peripheral information and coordinates cardiac rhythmic output has been elusive. Here, we show that kruppel-like factor 15 (KLF15) governs a biphasic transcriptomic oscillation in the heart with a maximum ATP production phase and a remodeling and repair phase corresponding to the active and resting phase of a rodent. Depletion of KLF15 in cardiomyocytes leads to a disorganized oscillatory behavior without phasic partition despite an intact core clock. Thus, KLF15 is a nodal connection between the clock and meaningful rhythmicity in the heart.
authors.affiliation: Case Cardiovascular Research Institute, Department of Medicine, Harrington Heart and Vascular Institute, University Hospitals Case Medical Center, Cleveland, OH 44106, USA; Department of Genetics and Genome Sciences, Case Western Reserve University, Cleveland, OH 44106, USA.
authors.forename: Lilei
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Case Cardiovascular Research Institute, Department of Medicine, Harrington Heart and Vascular Institute, University Hospitals Case Medical Center, Cleveland, OH 44106, USA.
authors.forename: Domenick A
authors.initials: DA
authors.lastname: Prosdocimo
authors.affiliation: Center for RNA Molecular Biology, Case Western Reserve University, Cleveland, OH 44106, USA.
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Bai
authors.affiliation: Department of Genetics and Genome Sciences, Case Western Reserve University, Cleveland, OH 44106, USA.
authors.forename: Chen
authors.initials: C
authors.lastname: Fu
authors.affiliation: Case Cardiovascular Research Institute, Department of Medicine, Harrington Heart and Vascular Institute, University Hospitals Case Medical Center, Cleveland, OH 44106, USA.
authors.forename: Rongli
authors.initials: R
authors.lastname: Zhang
authors.affiliation: Center for RNA Molecular Biology, Case Western Reserve University, Cleveland, OH 44106, USA.
authors.forename: Frank
authors.initials: F
authors.lastname: Campbell
authors.affiliation: Case Cardiovascular Research Institute, Department of Medicine, Harrington Heart and Vascular Institute, University Hospitals Case Medical Center, Cleveland, OH 44106, USA.
authors.forename: Xudong
authors.initials: X
authors.lastname: Liao
authors.affiliation: Center for RNA Molecular Biology, Case Western Reserve University, Cleveland, OH 44106, USA.
authors.forename: Jeff
authors.initials: J
authors.lastname: Coller
authors.affiliation: Case Cardiovascular Research Institute, Department of Medicine, Harrington Heart and Vascular Institute, University Hospitals Case Medical Center, Cleveland, OH 44106, USA. Electronic address: mukesh.jain2@case.edu.
authors.forename: Mukesh K
authors.initials: MK
authors.lastname: Jain
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000444:Aldehyde Dehydrogenase / Q000235:genetics / Q000378:metabolism; D000071396:Aldehyde Dehydrogenase, Mitochondrial; D000818:Animals; D002460:Cell Line; D002940:Circadian Rhythm / Q000502:physiology; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D051741:Kruppel-Like Transcription Factors; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009206:Myocardium / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000166:cytology / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1 / Q000235:genetics / Q000378:metabolism; D011401:Promoter Regions, Genetic; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D011987:Receptors, Steroid / Q000235:genetics / Q000378:metabolism; D011988:Receptors, Thyroid Hormone / Q000235:genetics / Q000378:metabolism; D017423:Sequence Analysis, RNA; D014157:Transcription Factors / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D059467:Transcriptome
chemical_list: D004268:DNA-Binding Proteins; C467418:Klf15 protein, mouse; D051741:Kruppel-Like Transcription Factors; D009419:Nerve Tissue Proteins; C539818:Nr4a1 protein, mouse; C490411:Nr4a3 protein, mouse; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1; D034741:RNA, Small Interfering; D011987:Receptors, Steroid; D011988:Receptors, Thyroid Hormone; D014157:Transcription Factors; D000255:Adenosine Triphosphate; C515029:ALDH2 protein, mouse; D000444:Aldehyde Dehydrogenase; D000071396:Aldehyde Dehydrogenase, Mitochondrial