Novel Roles for the Transcriptional Repressor E4BP4 in Both Cardiac Physiology and Pathophysiology

Sobuj Mia; Ravi Sonkar; Lamario Williams; Mary N. Latimer; David R. Rawnsley; Samir Rana; Jin He; Pieterjan Dierickx; Teayoun Kim; Min Xie; Kirk M. Habegger; Masato Kubo; Lufang Zhou; Morten B. Thomsen; Sumanth D. Prabhu; Stuart J. Frank; Paul S. Brookes; Mitchell A. Lazar; Abhinav Diwan; Martin E. Young

doi:10.1016/j.jacbts.2023.03.016

Novel Roles for the Transcriptional Repressor E4BP4 in Both Cardiac Physiology and Pathophysiology

Sobuj Mia, Ravi Sonkar, Lamario Williams, Mary N. Latimer, David R. Rawnsley, Samir Rana, Jin He, Pieterjan Dierickx, Teayoun Kim, Min Xie, Kirk M. Habegger, Masato Kubo, Lufang Zhou, Morten B. Thomsen, Sumanth D. Prabhu, Stuart J. Frank, Paul S. Brookes, Mitchell A. Lazar, Abhinav Diwan, Martin E. Young

Research output: Contribution to journal › Article › peer-review

11 Scopus citations

Abstract

Circadian clocks temporally orchestrate biological processes critical for cellular/organ function. For example, the cardiomyocyte circadian clock modulates cardiac metabolism, signaling, and electrophysiology over the course of the day, such that, disruption of the clock leads to age-onset cardiomyopathy (through unknown mechanisms). Here, we report that genetic disruption of the cardiomyocyte clock results in chronic induction of the transcriptional repressor E4BP4. Importantly, E4BP4 deletion prevents age-onset cardiomyopathy following clock disruption. These studies also indicate that E4BP4 regulates both cardiac metabolism (eg, fatty acid oxidation) and electrophysiology (eg, QT interval). Collectively, these studies reveal that E4BP4 is a novel regulator of both cardiac physiology and pathophysiology.

Original language	English
Pages (from-to)	1141-1156
Number of pages	16
Journal	JACC: Basic to Translational Science
Volume	8
Issue number	9
DOIs	https://doi.org/10.1016/j.jacbts.2023.03.016
State	Published - Sep 2023

Keywords

chronobiology
electrophysiology
heart failure
metabolism

Access to Document

10.1016/j.jacbts.2023.03.016

Cite this

Mia, S., Sonkar, R., Williams, L., Latimer, M. N., Rawnsley, D. R., Rana, S., He, J., Dierickx, P., Kim, T., Xie, M., Habegger, K. M., Kubo, M., Zhou, L., Thomsen, M. B., Prabhu, S. D., Frank, S. J., Brookes, P. S., Lazar, M. A., Diwan, A., & Young, M. E. (2023). Novel Roles for the Transcriptional Repressor E4BP4 in Both Cardiac Physiology and Pathophysiology. JACC: Basic to Translational Science, 8(9), 1141-1156. https://doi.org/10.1016/j.jacbts.2023.03.016

@article{dfd58ead798645a1ab0c87f0a57a4c13,

title = "Novel Roles for the Transcriptional Repressor E4BP4 in Both Cardiac Physiology and Pathophysiology",

abstract = "Circadian clocks temporally orchestrate biological processes critical for cellular/organ function. For example, the cardiomyocyte circadian clock modulates cardiac metabolism, signaling, and electrophysiology over the course of the day, such that, disruption of the clock leads to age-onset cardiomyopathy (through unknown mechanisms). Here, we report that genetic disruption of the cardiomyocyte clock results in chronic induction of the transcriptional repressor E4BP4. Importantly, E4BP4 deletion prevents age-onset cardiomyopathy following clock disruption. These studies also indicate that E4BP4 regulates both cardiac metabolism (eg, fatty acid oxidation) and electrophysiology (eg, QT interval). Collectively, these studies reveal that E4BP4 is a novel regulator of both cardiac physiology and pathophysiology.",

keywords = "chronobiology, electrophysiology, heart failure, metabolism",

author = "Sobuj Mia and Ravi Sonkar and Lamario Williams and Latimer, {Mary N.} and Rawnsley, {David R.} and Samir Rana and Jin He and Pieterjan Dierickx and Teayoun Kim and Min Xie and Habegger, {Kirk M.} and Masato Kubo and Lufang Zhou and Thomsen, {Morten B.} and Prabhu, {Sumanth D.} and Frank, {Stuart J.} and Brookes, {Paul S.} and Lazar, {Mitchell A.} and Abhinav Diwan and Young, {Martin E.}",

note = "Publisher Copyright: {\textcopyright} 2023 The Authors",

year = "2023",

month = sep,

doi = "10.1016/j.jacbts.2023.03.016",

language = "English",

volume = "8",

pages = "1141--1156",

journal = "JACC: Basic to Translational Science",

issn = "2452-302X",

number = "9",

}

Mia, S, Sonkar, R, Williams, L, Latimer, MN, Rawnsley, DR, Rana, S, He, J, Dierickx, P, Kim, T, Xie, M, Habegger, KM, Kubo, M, Zhou, L, Thomsen, MB, Prabhu, SD, Frank, SJ, Brookes, PS, Lazar, MA, Diwan, A & Young, ME 2023, 'Novel Roles for the Transcriptional Repressor E4BP4 in Both Cardiac Physiology and Pathophysiology', JACC: Basic to Translational Science, vol. 8, no. 9, pp. 1141-1156. https://doi.org/10.1016/j.jacbts.2023.03.016

TY - JOUR

T1 - Novel Roles for the Transcriptional Repressor E4BP4 in Both Cardiac Physiology and Pathophysiology

AU - Mia, Sobuj

AU - Sonkar, Ravi

AU - Williams, Lamario

AU - Latimer, Mary N.

AU - Rawnsley, David R.

AU - Rana, Samir

AU - He, Jin

AU - Dierickx, Pieterjan

AU - Kim, Teayoun

AU - Xie, Min

AU - Habegger, Kirk M.

AU - Kubo, Masato

AU - Zhou, Lufang

AU - Thomsen, Morten B.

AU - Prabhu, Sumanth D.

AU - Frank, Stuart J.

AU - Brookes, Paul S.

AU - Lazar, Mitchell A.

AU - Diwan, Abhinav

AU - Young, Martin E.

PY - 2023/9

Y1 - 2023/9

N2 - Circadian clocks temporally orchestrate biological processes critical for cellular/organ function. For example, the cardiomyocyte circadian clock modulates cardiac metabolism, signaling, and electrophysiology over the course of the day, such that, disruption of the clock leads to age-onset cardiomyopathy (through unknown mechanisms). Here, we report that genetic disruption of the cardiomyocyte clock results in chronic induction of the transcriptional repressor E4BP4. Importantly, E4BP4 deletion prevents age-onset cardiomyopathy following clock disruption. These studies also indicate that E4BP4 regulates both cardiac metabolism (eg, fatty acid oxidation) and electrophysiology (eg, QT interval). Collectively, these studies reveal that E4BP4 is a novel regulator of both cardiac physiology and pathophysiology.

AB - Circadian clocks temporally orchestrate biological processes critical for cellular/organ function. For example, the cardiomyocyte circadian clock modulates cardiac metabolism, signaling, and electrophysiology over the course of the day, such that, disruption of the clock leads to age-onset cardiomyopathy (through unknown mechanisms). Here, we report that genetic disruption of the cardiomyocyte clock results in chronic induction of the transcriptional repressor E4BP4. Importantly, E4BP4 deletion prevents age-onset cardiomyopathy following clock disruption. These studies also indicate that E4BP4 regulates both cardiac metabolism (eg, fatty acid oxidation) and electrophysiology (eg, QT interval). Collectively, these studies reveal that E4BP4 is a novel regulator of both cardiac physiology and pathophysiology.

KW - chronobiology

KW - electrophysiology

KW - heart failure

KW - metabolism

UR - http://www.scopus.com/inward/record.url?scp=85170535344&partnerID=8YFLogxK

U2 - 10.1016/j.jacbts.2023.03.016

DO - 10.1016/j.jacbts.2023.03.016

M3 - Article

C2 - 37791313

AN - SCOPUS:85170535344

SN - 2452-302X

VL - 8

SP - 1141

EP - 1156

JO - JACC: Basic to Translational Science

JF - JACC: Basic to Translational Science

IS - 9

ER -

Novel Roles for the Transcriptional Repressor E4BP4 in Both Cardiac Physiology and Pathophysiology

Abstract

Keywords

Access to Document

Other files and links

Fingerprint

Cite this