ArticleJournal of molecular and cellular cardiology2013
Lrrc10 is a novel cardiac-specific target gene of Nkx2-5 and GATA4.
Article in Journal of molecular and cellular cardiology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 30 citations in OpenAlex.
- A metabolic-epigenetic switch governs multicellular cardiac repair following succinate dehydrogenase inhibition.Nature cardiovascular research · 2026Article
- The Rab3 GTPase cycle modulates cardiomyocyte exocytosis and atrial natriuretic peptide release.Biophysical journal · 2025Article
- Rab3gap1 palmitoylation cycling modulates cardiomyocyte exocytosis and atrial natriuretic peptide release.Biophysical journal · 2025Article
- Cardiac L-type calcium channel regulation by Leucine-Rich Repeat-Containing Protein 10.Channels (Austin, Tex.) · 2024Review
- Article
- Unveiling the Spectrum of Minor Genes in Cardiomyopathies: A Narrative Review.International journal of molecular sciences · 2024Review
- Disruption of valosin-containing protein activity causes cardiomyopathy and reveals pleiotropic functions in cardiac homeostasis.The Journal of biological chemistry · 2019Article
- Oligogenic inheritance of a human heart disease involving a genetic modifier.Science (New York, N.Y.) · 2019Article
- Myocardial-specific ablation ofThe Journal of biological chemistry · 2019Article
- Cardiac-specific developmental and epigenetic functions of Jarid2 during embryonic development.The Journal of biological chemistry · 2018Article
- Defective Flux of Thrombospondin-4 through the Secretory Pathway Impairs Cardiomyocyte Membrane Stability and Causes Cardiomyopathy.Molecular and cellular biology · 2018Article
- Computational modeling suggests impaired interactions between NKX2.5 and GATA4 in individuals carrying a novel pathogenic D16N NKX2.5 mutation.Oncotarget · 2018Article
- Genome-Wide Temporal Profiling of Transcriptome and Open Chromatin of Early Cardiomyocyte Differentiation Derived From hiPSCs and hESCs.Circulation research · 2017Article
- Molecular pathological study on LRRC10 in sudden unexplained nocturnal death syndrome in the Chinese Han population.International journal of legal medicine · 2017Article
- LRRC10 is required to maintain cardiac function in response to pressure overload.American journal of physiology. Heart and circulatory physiology · 2016Article
- Dissection of Thrombospondin-4 Domains Involved in Intracellular Adaptive Endoplasmic Reticulum Stress-Responsive Signaling.Molecular and cellular biology · 2016Article
- The Role of Leucine-Rich Repeat Containing Protein 10 (LRRC10) in Dilated Cardiomyopathy.Frontiers in physiology · 2016Review
- MicroRNA and mRNA signatures in ischemia reperfusion injury in heart transplantation.PloS one · 2013Article
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Cardiac gene expression is precisely regulated and its perturbation causes developmental defects and heart disease. Leucine-rich repeat containing 10 (Lrrc10) is a cardiac-specific factor that is crucial for proper cardiac development and deletion of Lrrc10 in mice results in dilated cardiomyopathy. However, the mechanisms regulating Lrrc10 expression in cardiomyocytes remain unknown. Therefore, we set out to determine trans-acting factors and cis-elements critical for mediating Lrrc10 expression. We identify Lrrc10 as a transcriptional target of Nkx2-5 and GATA4. The Lrrc10 promoter region contains two highly conserved cardiac regulatory elements, which are functional in cardiomyocytes but not in fibroblasts. In vivo, Nkx2-5 and GATA4 endogenously occupy the proximal and distal cardiac regulatory elements of Lrrc10 in the heart. Moreover, embryonic hearts of Nkx2-5 knockout mice have dramatically reduced expression of Lrrc10. These data demonstrate the importance of Nkx2-5 and GATA4 in regulation of Lrrc10 expression in vivo. The proximal cardiac regulatory element located at around -200bp is synergistically activated by Nkx2-5 and GATA4 while the distal cardiac regulatory element present around -3kb requires SRF in addition to Nkx2-5 and GATA4 for synergistic activation. Mutational analyses identify a pair of adjacent Nkx2-5 and GATA binding sites within the proximal cardiac regulatory element that are necessary to induce expression of Lrrc10. In contrast, only the GATA site is functional in the distal regulatory element. Taken together, our data demonstrate that the transcription factors Nkx2-5 and GATA4 cooperatively regulate cardiac-specific expression of Lrrc10.
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