ArticleNucleic acids research2013
Megakaryocytic leukemia 1 (MKL1) ties the epigenetic machinery to hypoxia-induced transactivation of endothelin-1.
Article in Nucleic acids research, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 53 citations in OpenAlex.
- Article
- Article
- A GSK3-SRF Axis Mediates Angiotensin II Induced Endothelin Transcription in Vascular Endothelial Cells.Frontiers in cell and developmental biology · 2021Article
- The Jumonji Domain-Containing Histone Demethylase Homolog 1D/lysine Demethylase 7A (JHDM1D/KDM7A) Is an Epigenetic Activator of RHOJ Transcription in Breast Cancer Cells.Frontiers in cell and developmental biology · 2021Article
- Myeloid MKL1 Disseminates Cues to Promote Cardiac Hypertrophy in Mice.Frontiers in cell and developmental biology · 2021Article
- Myocardin-Related Transcription Factor A Mediates LPS-Induced iNOS Transactivation.Inflammation · 2020Article
- Dual roles of chromatin remodeling protein BRG1 in angiotensin II-induced endothelial-mesenchymal transition.Cell death & disease · 2020Article
- Activation of TWIST Transcription by Chromatin Remodeling Protein BRG1 Contributes to Liver Fibrosis in Mice.Frontiers in cell and developmental biology · 2020Article
- BRG1 ActivatesFrontiers in cell and developmental biology · 2020Article
- BRG1 Stimulates Endothelial Derived Alarmin MRP8 to Promote Macrophage Infiltration in an Animal Model of Cardiac Hypertrophy.Frontiers in cell and developmental biology · 2020Article
- Ablation of serum response factor in hepatic stellate cells attenuates liver fibrosis.Journal of molecular medicine (Berlin, Germany) · 2019Article
- Serum response factor (SRF) promotes ROS generation and hepatic stellate cell activation by epigenetically stimulating NCF1/2 transcription.Redox biology · 2019Article
- MKL1 mediates TNF-α induced pro-inflammatory transcription by bridging the crosstalk between BRG1 and WDR5.Journal of biomedical research · 2019Article
- Precision medicine and personalising therapy in pulmonary hypertension: seeing the light from the dawn of a new era.European respiratory review : an official journal of the European Respiratory Society · 2018Review
- Critical effects of epigenetic regulation in pulmonary arterial hypertension.Cellular and molecular life sciences : CMLS · 2017Review
- HDAC4 stimulates MRTF-A expression and drives fibrogenesis in hepatic stellate cells by targeting miR-206.Oncotarget · 2017Article
- MKL1 defines the H3K4Me3 landscape for NF-κB dependent inflammatory response.Scientific reports · 2017Article
- MKL1 potentiates lung cancer cell migration and invasion by epigenetically activating MMP9 transcription.Oncogene · 2015Article
- Mechanism of irradiation-induced mammary cancer metastasis: A role for SAP-dependent Mkl1 signaling.Molecular oncology · 2015Article
- A Role of Myocardin Related Transcription Factor-A (MRTF-A) in Scleroderma Related Fibrosis.PloS one · 2015Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Increased synthesis of endothelin-1 (ET-1) by human vascular endothelial cells (HVECs) in response to hypoxia underscores persistent vasoconstriction observed in patients with pulmonary hypertension. The molecular mechanism whereby hypoxia stimulates ET-1 gene transcription is not well understood. Here we report that megakaryocytic leukemia 1 (MKL1) potentiated hypoxia-induced ET-1 transactivation in HVECs. Disruption of MKL1 activity by either a dominant negative mutant or small interfering RNA mediated knockdown dampened ET-1 synthesis. MKL1 was recruited to the proximal ET-1 promoter region (-81/+150) in HVECs challenged with hypoxic stress by the sequence-specific transcription factor serum response factor (SRF). Depletion of SRF blocked MKL1 recruitment and blunted ET-1 transactivation by hypoxia. Chromatin immunoprecipitation analysis of the ET-1 promoter revealed that MKL1 loss-of-function erased histone modifications consistent with transcriptional activation. In addition, MKL1 was indispensable for the occupancy of Brg1 and Brm, key components of the chromatin remodeling complex, on the ET-1 promoter. Brg1 and Brm modulated ET-1 transactivation by impacting histone modifications. In conclusion, our data have delineated a MKL1-centered complex that links epigenetic maneuverings to ET-1 transactivation in HVECs under hypoxic conditions.
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