miR-1 modulates HDAC4, calmodulin and MAPK1/Erk2 during early atrial differentiation
Abstract Funding Acknowledgements None. Introduction A large diversity of epigenetic factors, such as microRNAs and histones modifications, are known to be capable of regulating gene expression without altering DNA sequence itself. In particular, miR-1 is considered the first essential microRNA in c...
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Published in | Cardiovascular research Vol. 120; no. Supplement_1 |
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Main Authors | , , , , , , |
Format | Journal Article |
Language | English |
Published |
US
Oxford University Press
29.05.2024
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Online Access | Get full text |
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Summary: | Abstract
Funding Acknowledgements
None.
Introduction
A large diversity of epigenetic factors, such as microRNAs and histones modifications, are known to be capable of regulating gene expression without altering DNA sequence itself. In particular, miR-1 is considered the first essential microRNA in cardiac development.
Purpose
The aim of this work is to analyze the miR-1 modulation role in cardiac chamber differentiation through specific signaling pathways.
Methods
By means of microinjections in both primitive endocardial tubes of chick embryo culture, gain- and loss-of-function experiments were performed with premiR-1 and anti-miR-1, respectively. Subsequently, embryos were subjected to whole mount in situ hybridization with Tbx5, Gata4 and AMHC1 probes, as well as immunohistochemistry with Mef2c, HDAC4, Calmodulin/Calm1 and MAPK1/Erk2 antibodies. Also, we carried out RT-qPCR analysis of control and experimental embryos, including CRABPI, CRABPII and retinoic acid receptors (RAR and RXR).
Results
Our results reveal that miR-1 increases specific atrial gene expression such as Tbx5, Gata4 and AMHC1, while this microRNA diminishes Mef2c expression. Furthermore, we observed that miR-1 upregulates CRABPII and RARß, and downregulates CRABPI, which are three crucial factors in retinoic acid signaling pathway. Interestingly, we also observed that miR-1 actively interacts with HDAC4, Calmodulin and Erk2/MAPK1, key factors involved in Mef2c regulation.
Conclusion
All these data suggest that miR-1 functions as an epigenetic factor modulating complementary actions performed by retinoic acid and Mef2c, which are required to properly assign cells as sinoatrial precursors. |
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ISSN: | 0008-6363 1755-3245 |
DOI: | 10.1093/cvr/cvae088.001 |