Critical role of Znhit1 for postnatal heart function and vacuolar cardiomyopathy
Ca2+ is critical for cardiac electrical conduction and contractility, and aberrant Ca2+ homeostasis causes arrhythmia and heart failure. Chromatin remodeling modulates gene expression involved in cardiac sarcomere assembly and postnatal heart function. However, the chromatin-remodeling regulatory me...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
American Society for Clinical investigation
2022-03-01
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| Series: | JCI Insight |
| Subjects: | |
| Online Access: | https://doi.org/10.1172/jci.insight.148752 |
| _version_ | 1828808194533621760 |
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| author | Yingchao Shi Wenli Fan Mingjie Xu Xinhua Lin Wukui Zhao Zhongzhou Yang |
| author_facet | Yingchao Shi Wenli Fan Mingjie Xu Xinhua Lin Wukui Zhao Zhongzhou Yang |
| author_sort | Yingchao Shi |
| collection | DOAJ |
| description | Ca2+ is critical for cardiac electrical conduction and contractility, and aberrant Ca2+ homeostasis causes arrhythmia and heart failure. Chromatin remodeling modulates gene expression involved in cardiac sarcomere assembly and postnatal heart function. However, the chromatin-remodeling regulatory mechanism of cardiac Ca2+ homeostasis is unknown. Here, we found that Znhit1, a core subunit of the SRCAP remodeling complex, was essential for heart function. Deletion of Znhit1 in postnatal hearts of mice resulted in arrhythmia, idiopathic vacuolar cardiomyopathy, rapid heart failure, and premature sudden death. In addition, the level of Casq1, a sarcoplasmic reticulum Ca2+ regulatory protein, was massively elevated while SERCA2a showed reduced protein level. Mechanistically, the Znhit1 modulated the expression of Casq1 and SERCA2a by depositing H2A.Z at their promoters. Deletion of Casq1 could substantially alleviate the vacuolar formation in Znhit1 Casq1 KO mice. These findings demonstrate that Znhit1 is required for postnatal heart function and maintains cardiac Ca2+ homeostasis and that accumulation of Casq1 might be a causative factor for vacuolar cardiomyopathy. |
| first_indexed | 2024-12-12T08:37:06Z |
| format | Article |
| id | doaj.art-797b8a97550146a89d2a9cbb4bd5d61c |
| institution | Directory Open Access Journal |
| issn | 2379-3708 |
| language | English |
| last_indexed | 2024-12-12T08:37:06Z |
| publishDate | 2022-03-01 |
| publisher | American Society for Clinical investigation |
| record_format | Article |
| series | JCI Insight |
| spelling | doaj.art-797b8a97550146a89d2a9cbb4bd5d61c2022-12-22T00:30:54ZengAmerican Society for Clinical investigationJCI Insight2379-37082022-03-0176Critical role of Znhit1 for postnatal heart function and vacuolar cardiomyopathyYingchao ShiWenli FanMingjie XuXinhua LinWukui ZhaoZhongzhou YangCa2+ is critical for cardiac electrical conduction and contractility, and aberrant Ca2+ homeostasis causes arrhythmia and heart failure. Chromatin remodeling modulates gene expression involved in cardiac sarcomere assembly and postnatal heart function. However, the chromatin-remodeling regulatory mechanism of cardiac Ca2+ homeostasis is unknown. Here, we found that Znhit1, a core subunit of the SRCAP remodeling complex, was essential for heart function. Deletion of Znhit1 in postnatal hearts of mice resulted in arrhythmia, idiopathic vacuolar cardiomyopathy, rapid heart failure, and premature sudden death. In addition, the level of Casq1, a sarcoplasmic reticulum Ca2+ regulatory protein, was massively elevated while SERCA2a showed reduced protein level. Mechanistically, the Znhit1 modulated the expression of Casq1 and SERCA2a by depositing H2A.Z at their promoters. Deletion of Casq1 could substantially alleviate the vacuolar formation in Znhit1 Casq1 KO mice. These findings demonstrate that Znhit1 is required for postnatal heart function and maintains cardiac Ca2+ homeostasis and that accumulation of Casq1 might be a causative factor for vacuolar cardiomyopathy.https://doi.org/10.1172/jci.insight.148752Cardiology |
| spellingShingle | Yingchao Shi Wenli Fan Mingjie Xu Xinhua Lin Wukui Zhao Zhongzhou Yang Critical role of Znhit1 for postnatal heart function and vacuolar cardiomyopathy JCI Insight Cardiology |
| title | Critical role of Znhit1 for postnatal heart function and vacuolar cardiomyopathy |
| title_full | Critical role of Znhit1 for postnatal heart function and vacuolar cardiomyopathy |
| title_fullStr | Critical role of Znhit1 for postnatal heart function and vacuolar cardiomyopathy |
| title_full_unstemmed | Critical role of Znhit1 for postnatal heart function and vacuolar cardiomyopathy |
| title_short | Critical role of Znhit1 for postnatal heart function and vacuolar cardiomyopathy |
| title_sort | critical role of znhit1 for postnatal heart function and vacuolar cardiomyopathy |
| topic | Cardiology |
| url | https://doi.org/10.1172/jci.insight.148752 |
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