Jund orchestrates cis- regulatory element dynamics to facilitate endothelial- to- hematopoietic transition

• 成果类型: Article
• 署名作者: Guo, Jiani; Liu, Mengyao; Liu, Feng; Wang, Lu
• 署名单位: Chinese Academy of Medical Sciences - Peking Union Medical College; Institute of Hematology & Blood Diseases Hospital - CAMS; Peking Union Medical College; Chinese Academy of Sciences; University of Chinese Academy of Sciences, CAS; Institute of Zoology, CAS
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-9643
• DOI: 10.1073/pnas.2426714122
• 发表日期: 2025-06-10
• 关键词: transcription factors; aortic endothelium; stem; promoter; ap-1; activation; chromatin; mechanisms; macrophage; migration

摘要

The tightly controlled spatiotemporal expression of developmental genes depends on the concerted action of cis-regulatory elements (CREs) and transcription factors (TFs) to ensure cell fate decisions. Endothelial-to-hematopoietic transition (EHT) is a cell fate transition process by which endothelial cells acquire hematopoietic identity and become hemogenic endothelial cells (HECs) and then hematopoietic stem and progenitor cells, but the underlying CRE network dynamics and its regulation by TFs remain unclear. In this study, we characterized the dynamics of CRE activation and TF occupancy during zebrafish EHT, and found that the enhancer-promoter collaboration forms the basis for EHT. Moreover, a ubiquitously expressed TF AP-1 collaborates with diverse lineage-specific TFs to remodel enhancer landscape. Deletion of AP-1 family member Jund impaired hematopoietic specification, resulting from the enhanced endothelial identity in the HEC. Mechanistically, Jund and hematopoietic TF Hoxa9a collectively repress the activity of an endothelial-related dll4 enhancer through tight control of the active histone modification H3K27ac. Our study provides insights into the cooperative function among ubiquitous TFs and cell type-specific TFs in orchestrating cell fate transition.