KLF15 Establishes the Landscape of Diurnal Expression in the Heart
Lilei Zhang,
Domenick A. Prosdocimo,
Xiaodong Bai,
Chen Fu,
Rongli Zhang,
Frank Campbell,
Xudong Liao,
Jeff Coller,
Mukesh K. Jain
Affiliations
Lilei Zhang
Case Cardiovascular Research Institute, Department of Medicine, Harrington Heart and Vascular Institute, University Hospitals Case Medical Center, Cleveland, OH 44106, USA
Domenick A. Prosdocimo
Case Cardiovascular Research Institute, Department of Medicine, Harrington Heart and Vascular Institute, University Hospitals Case Medical Center, Cleveland, OH 44106, USA
Xiaodong Bai
Center for RNA Molecular Biology, Case Western Reserve University, Cleveland, OH 44106, USA
Chen Fu
Department of Genetics and Genome Sciences, Case Western Reserve University, Cleveland, OH 44106, USA
Rongli Zhang
Case Cardiovascular Research Institute, Department of Medicine, Harrington Heart and Vascular Institute, University Hospitals Case Medical Center, Cleveland, OH 44106, USA
Frank Campbell
Center for RNA Molecular Biology, Case Western Reserve University, Cleveland, OH 44106, USA
Xudong Liao
Case Cardiovascular Research Institute, Department of Medicine, Harrington Heart and Vascular Institute, University Hospitals Case Medical Center, Cleveland, OH 44106, USA
Jeff Coller
Center for RNA Molecular Biology, Case Western Reserve University, Cleveland, OH 44106, USA
Mukesh K. Jain
Case Cardiovascular Research Institute, Department of Medicine, Harrington Heart and Vascular Institute, University Hospitals Case Medical Center, Cleveland, OH 44106, USA
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.
