2. Academic Validation
  3. Enforced activation of the CREB/KDM2B axis prevents alcohol-induced embryonic developmental delay

Enforced activation of the CREB/KDM2B axis prevents alcohol-induced embryonic developmental delay

  • Cell Rep. 2024 Dec 24;43(12):115075. doi: 10.1016/j.celrep.2024.115075.
Hang Liu 1,  Qiyu Ren 2,  Meihan Gong 1,  Feifei Zuo 1,  Qian Li 1,  Dawei Huo 3,  Ye Yuan 1,  Yutong Zhang 2,  Yu Kong 1,  Xiaozhi Liu 4,  Cailing Lu 5,  Xudong Wu 6
Affiliations

Affiliations

  • 1 State Key Laboratory of Experimental Hematology, the Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), Tianjin Key Laboratory of Medical Epigenetics, Department of Cell Biology, Tianjin Medical University, Qixiangtai Road 22, Tianjin 300070, China.
  • 2 Department of Genetics, National Research Institute for Family Planning, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100081, China.
  • 3 State Key Laboratory of Experimental Hematology, the Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), Tianjin Key Laboratory of Medical Epigenetics, Department of Cell Biology, Tianjin Medical University, Qixiangtai Road 22, Tianjin 300070, China; Bone Marrow Transplantation Center, the First Affiliated Hospital, Zhejiang University School of Medicine, Liangzhu Laboratory, Institute of Hematology, Zhejiang University, Hangzhou 311113, China.
  • 4 Tianjin Key Laboratory of Epigenetics for Organ Development of Premature Infants, Tianjin 300450, China.
  • 5 Department of Genetics, National Research Institute for Family Planning, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100081, China. Electronic address: lucailing@nrifp.org.cn.
  • 6 State Key Laboratory of Experimental Hematology, the Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), Tianjin Key Laboratory of Medical Epigenetics, Department of Cell Biology, Tianjin Medical University, Qixiangtai Road 22, Tianjin 300070, China; Tianjin Key Laboratory of Epigenetics for Organ Development of Premature Infants, Tianjin 300450, China. Electronic address: wuxudong@tmu.edu.cn.
PMID: 39661511 DOI: 10.1016/j.celrep.2024.115075
Abstract

Unintentional, early pregnancy alcohol consumption affects embryonic development. During the peri-implantation stage, coinciding with the transition from naive to primed pluripotency, the long isoform of KDM2B (KDM2BLF) underlies the de novo establishment of polycomb repressive complex (PRC) functions at promoters after fertilization. However, it remains unclear whether and how ethanol exposure affects this spatiotemporal chromatin setting. Here, we show that exposing peri-implantation mouse embryos to ethanol leads to impaired post-implantation development, mirrored by the delayed exit of naive pluripotency in acetaldehyde-treated embryonic stem cells. Remarkably, these abnormalities are linked to inadequate KDM2BLF expression and compromised deposition of PRC marks, which arise from cAMP response element-binding protein (CREB) inactivation. Accordingly, pharmacological activation of CREB effectively restores pluripotency transition partly dependent on KDM2BLF in vitro and ameliorates post-implantation embryonic defects in vivo. Therefore, our study highlights the pivotal role of the CREB/KDM2B axis in chromatin configuration and developmental programming, proposing potential preventive strategies against ethanol exposure-induced detrimental effects.

Keywords

CP: Developmental biology; CP: Molecular biology; CREB; H3K27me3; KDM2B; PDE4 inhibitor; PRC2; acetaldehyde; ethanol exposure; pluripotency; polycomb; post-implantation.

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