The core circadian clock factor, Bmal1, transduces sex-specific differences in both rhythmic and non-rhythmic gene expression in the mouse heart.

Autor:	Zhang X; Department of Physiology and Aging, University of Florida, Gainesville FL, United States., Procopio SB; Department of Physiology and Aging, University of Florida, Gainesville FL, United States., Ding H; Department of Biostatics, University of Florida, Gainesville FL, United States., Semel MG; Department of Physiology and Aging, University of Florida, Gainesville FL, United States., Schroder EA; Department of Physiology, University of Kentucky, Lexington, KY, United States.; Department of Internal Medicine, University of Kentucky, Lexington, KY, United States., Viggars MR; Department of Physiology and Aging, University of Florida, Gainesville FL, United States., Seward TS; Department of Physiology, University of Kentucky, Lexington, KY, United States., Du P; Department of Physiology and Aging, University of Florida, Gainesville FL, United States., Wu K; Department of Physiology and Aging, University of Florida, Gainesville FL, United States., Johnson SR; Department of Physiology, University of Kentucky, Lexington, KY, United States., Prabhat A; Department of Physiology, University of Kentucky, Lexington, KY, United States., Schneider DJ; Department of Physiology, University of Kentucky, Lexington, KY, United States., Stumpf IG; Department of Physiology, University of Kentucky, Lexington, KY, United States., Rozmus ER; Department of Physiology, University of Kentucky, Lexington, KY, United States., Huo Z; Department of Biostatics, University of Florida, Gainesville FL, United States., Delisle BP; Department of Physiology, University of Kentucky, Lexington, KY, United States., Esser KA; Department of Physiology and Aging, University of Florida, Gainesville FL, United States.
Jazyk:	angličtina
Zdroj:	Function (Oxford, England) [Function (Oxf)] 2024 Dec 10. Date of Electronic Publication: 2024 Dec 10.
DOI:	10.1093/function/zqae053
Abstrakt:	It has been well established that cardiovascular diseases exhibit significant differences between sexes in both preclinical models and humans. In addition, there is growing recognition that disrupted circadian rhythms can contribute to the onset and progression of cardiovascular diseases. However, little is known about sex differences between the cardiac circadian clock and circadian transcriptomes in mice. Here, we show that the core clock genes are expressed in common in both sexes, but the cardiac circadian transcriptome is very sex specific. Hearts from female mice expressed significantly more rhythmically expressed genes (REGs) than male hearts, and the temporal distribution of REGs was distinctly different between sexes. To test the contribution of the circadian clock in sex-specific gene expression in the heart, we knocked out the core circadian clock factor Bmal1 in adult cardiomyocytes. The sex differences in the circadian transcriptomes were significantly diminished with cardiomyocyte-specific loss of Bmal1. Surprisingly, loss of cardiomyocyte Bmal1 also resulted in a roughly 8-fold reduction in the number of all differentially expressed genes (DEGs) between male and female hearts. We highlight sex-specific changes in several cardiac-specific transcription factors, including Gata4, Nkx2-5 and Tbx5. While there is still much to learn, we conclude that cardiomyocyte-specific Bmal1 is vital in conferring sex-specific gene expression in the adult mouse heart. (© The Author(s) 2024. Published by Oxford University Press on behalf of American Physiological Society.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu