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^*

^*Corresponding author for this work

Physiology of circulation, kidney and lung

Research output: Contribution to journal › Journal article › Research › peer-review

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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
Journal	JACC: Basic to Translational Science
Volume	8
Issue number	9
Pages (from-to)	1141-1156
Number of pages	16
ISSN	2452-302X
DOIs	https://doi.org/10.1016/j.jacbts.2023.03.016
Publication status	Published - 2023

Bibliographical note

Publisher Copyright:
© 2023 The Authors

Keywords

chronobiology
electrophysiology
heart failure
metabolism

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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

Novel Roles for the Transcriptional Repressor E4BP4 in Both Cardiac Physiology and Pathophysiology. / Mia, Sobuj; Sonkar, Ravi; Williams, Lamario; Latimer, Mary N.; Rawnsley, David R.; Rana, Samir; He, Jin; Dierickx, Pieterjan; Kim, Teayoun; Xie, Min; Habegger, Kirk M.; Kubo, Masato; Zhou, Lufang; Thomsen, Morten B.; Prabhu, Sumanth D.; Frank, Stuart J.; Brookes, Paul S.; Lazar, Mitchell A.; Diwan, Abhinav; Young, Martin E.

In: JACC: Basic to Translational Science, Vol. 8, No. 9, 2023, p. 1141-1156.

Research output: Contribution to journal › Journal article › Research › peer-review

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

Mia, Sobuj ; Sonkar, Ravi ; Williams, Lamario ; Latimer, Mary N. ; Rawnsley, David R. ; Rana, Samir ; He, Jin ; Dierickx, Pieterjan ; Kim, Teayoun ; Xie, Min ; Habegger, Kirk M. ; Kubo, Masato ; Zhou, Lufang ; Thomsen, Morten B. ; Prabhu, Sumanth D. ; Frank, Stuart J. ; Brookes, Paul S. ; Lazar, Mitchell A. ; Diwan, Abhinav ; Young, Martin E. / Novel Roles for the Transcriptional Repressor E4BP4 in Both Cardiac Physiology and Pathophysiology. In: JACC: Basic to Translational Science. 2023 ; Vol. 8, No. 9. pp. 1141-1156.

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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.",

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AU - Zhou, Lufang

AU - Thomsen, Morten B.

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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.

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