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ETV2/ER71 regulates hematovascular lineage generation and vascularization through an H3K9 demethylase, KDM4A

Year: 2024
Type: article
Abstract: Summary ETV2/ER71, an ETS (E-twenty six) transcription factor, is critical for hematopoiesis and vascular development. However, research about the molecular mechanisms behind ETV2-mediated gene transcription is limited. Herein, we demonstrate that ETV2 and KDM4A, an H3K9 demethylase, regulate hematopoietic and endothelial genes. Etv2−/− mouse embryonic stem cells (mESCs), which fail to generate hematopoietic and endothelial cells, exhibit enhanced H3K9me3 levels in hematopoietic and endothelial genes. ETV2 interacts with KDM4A, and the ETV2-mediated transcriptional activation of hematopoietic and endothelial genes depends on KDM4A histone demethylase activity. The ETV2 and KDM4A complex binds to the transcription regulatory regions of genes directly regulated by ETV2. Mice lacking Kdm4a and Etv2 in endothelial cells (Cdh5Cre:Kdm:Etv2f/f mice) display a more severe perfusion recovery and neovascularization defect, compared with Cdh5Cre:Kdm4af/f mice, Cdh5Cre:Etv2f/f mice, and controls. Collectively, we demonstrate that ETV2 interacts with KDM4A, and that this interaction is critical for hematovascular lineage generation and vascular regeneration.
Source: iScience
DOI: 10.1016/j.isci.2024.111538
Authors: Min Seong Kim, Raham Lee, Dong Hun Lee, Heesang Song, Taekyung Ha, Joo Kyung Kim, Bum-Yong Kang, Karl Agger, Kristian Helin, Donghyun Shin, Yunhee Kang, Changwon Park
Institutions: Louisiana State University, Emory University, Louisiana State University Health Sciences Center Shreveport, Chonnam National University, Chosun University, University of Copenhagen, Novo Nordisk Foundation, Memorial Sloan Kettering Cancer Center, Jeonbuk National University
Language: English
Open Access status: gold
Estimated APC paid: $3,150
Funders: Memorial Sloan-Kettering Cancer Center, Kræftens Bekæmpelse, Children's Healthcare of Atlanta, Children's Miracle Network Hospitals, National Research Foundation, National Research Foundation of Korea, Novo Nordisk Fonden, National Institutes of Health, School of Medicine, Emory University, National Heart, Lung, and Blood Institute, National Cancer Institute, Nevada Nurses Foundation
Awards: G2051006376, G289723095, G3308670482, G3589578894, G3939340782, G424654124, G4299475169, G5574875702, G602567894, G627736913, G7596307874, The Role of PPARy in the Pathogenesis and Therapy of Sickle Cell Disease-Pulmonary Hypertension, G8652864792, G9000003249, G9000304701, Cancer Center Support Grant
OpenAlex ID: W4405122685
FWCI: 0.577
Cites: 65
Cited by: 5
Related to: 10