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

doi:10.1016/j.celrep.2015.11.038

KLF15 Establishes the Landscape of Diurnal Expression in the Heart

Cell Rep. 2015 Dec 22;13(11):2368-2375. doi: 10.1016/j.celrep.2015.11.038. Epub 2015 Dec 10.

Authors

Lilei Zhang¹, Domenick A Prosdocimo², Xiaodong Bai³, Chen Fu⁴, Rongli Zhang², Frank Campbell³, Xudong Liao², Jeff Coller³, Mukesh K Jain⁵

Affiliations

¹ 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.
² Case Cardiovascular Research Institute, Department of Medicine, Harrington Heart and Vascular Institute, University Hospitals Case Medical Center, Cleveland, OH 44106, USA.
³ Center for RNA Molecular Biology, Case Western Reserve University, Cleveland, OH 44106, USA.
⁴ Department of Genetics and Genome Sciences, Case Western Reserve University, Cleveland, OH 44106, USA.
⁵ 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.

PMID: 26686628
DOI: 10.1016/j.celrep.2015.11.038

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.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Adenosine Triphosphate / metabolism
Aldehyde Dehydrogenase / genetics
Aldehyde Dehydrogenase / metabolism
Aldehyde Dehydrogenase, Mitochondrial
Animals
Cell Line
Circadian Rhythm / physiology
DNA-Binding Proteins / antagonists & inhibitors
DNA-Binding Proteins / genetics*
DNA-Binding Proteins / metabolism
Kruppel-Like Transcription Factors
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Myocardium / metabolism*
Myocytes, Cardiac / cytology
Myocytes, Cardiac / metabolism
Nerve Tissue Proteins / genetics
Nerve Tissue Proteins / metabolism
Nuclear Receptor Subfamily 4, Group A, Member 1 / genetics
Nuclear Receptor Subfamily 4, Group A, Member 1 / metabolism
Promoter Regions, Genetic
RNA Interference
RNA, Small Interfering / metabolism
Receptors, Steroid / genetics
Receptors, Steroid / metabolism
Receptors, Thyroid Hormone / genetics
Receptors, Thyroid Hormone / metabolism
Sequence Analysis, RNA
Transcription Factors / antagonists & inhibitors
Transcription Factors / genetics*
Transcription Factors / metabolism
Transcriptome

Substances

DNA-Binding Proteins
Klf15 protein, mouse
Kruppel-Like Transcription Factors
Nerve Tissue Proteins
Nr4a1 protein, mouse
Nr4a3 protein, mouse
Nuclear Receptor Subfamily 4, Group A, Member 1
RNA, Small Interfering
Receptors, Steroid
Receptors, Thyroid Hormone
Transcription Factors
Adenosine Triphosphate
ALDH2 protein, mouse
Aldehyde Dehydrogenase
Aldehyde Dehydrogenase, Mitochondrial

Abstract

Publication types

MeSH terms

Substances

Grants and funding