Excessive DNA Double‐Strand Breaks–Associated 3D Genome Reorganization Contributes to Neural Tube Defects with Folate Deficiency

Ting Zhang; Lin Lin; Jianting Li; Caihua Li; Shengjun Liang; Xuemei Bai; Fang Wang; Yihua Bao; Dan Guo; Xiaochen Bo; Hao Li; Hebing Chen; Qiu Xie

doi:10.1002/advs.202410603

journal article·2025-12Open access

Excessive DNA Double‐Strand Breaks–Associated 3D Genome Reorganization Contributes to Neural Tube Defects with Folate Deficiency

Ting Zhang, Lin Lin, Jianting Li, Caihua Li, Shengjun Liang, Xuemei Bai, Fang Wang, Yihua Bao, Dan Guo, Xiaochen Bo, Hao Li, Hebing Chen, Qiu Xie

Advanced Science· Volume 12· Issue 47

Publisher page Open full text

Source abstract

Abstract

Abstract Neural tube defects (NTDs) are one of the most common congenital malformations. Folic acid deficiency in pregnant women increases the risk of developing NTDs; however, the underlying etiology and mechanisms remain elusive. In this study, the role of DNA double‐strand breaks (DSBs) in 3D genome organization in NTDs with folate deficiency is reported. The NTD mouse model is burdened with abundant DSBs associated with the disruption of 3D genome organization. DSBs occurring in active genes lead to the stalling of RNA polymerase II (Pol II) and formation of R‐loops in the 3D genome. The DSB ratios of the genomic regions negatively correlated with the distance from the transcription start sites of the gene. The DSB ratios of the proximal and distal enhancers are significantly higher and induce the displacement of loops with busy anchors. Furthermore, DSB‐associated dysregulation of chromatin loops occurs in neural tube closure–associated genes that are abnormally expressed in human NTDs. Taken together, excessive DSB‐associated 3D genome organization disruption within NTDs with folate deficiency contributes to the dysregulation of neural tube closure–associated genes.

Source: crossref · Quality: baseline

Research context

Polymers

OpenAlex topics: Prenatal Screening and Diagnostics · Genomics and Chromatin Dynamics · Genomic variations and chromosomal abnormalities

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

Capital Center for Children's Health Capital Medical University Capital Institute of Pediatrics Beijing 100020 China

Institute of Health Service and Transfusion Medicine Beijing 100850 China

School of Computer Science and Information Technology& KLAS Northeast Normal University Beijing 100730 China

Department of Biochemistry and Molecular Biology College of Basic Medicine Shanxi Key Laboratory of Birth Defect and Cell Regeneration MOE Key Laboratory of Coal Environmental Pathogenicity and Prevention Taiyuan 030001 China

Shanghai GeneCowin Biotechnology Co. Ltd. Shanghai 200120 China

Department of Children's and Adolescent Health Public Health College Harbin Medical University Harbin 150081 China

Center for Biomedical Technology Institute of Clinical Medicine Peking Union Medical College Hospital Chinese Academy of Medical Sciences Beijing 100730 China

State Key Laboratory of Complex Severe and Rare Diseases Peking Union Medical College Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Beijing 100850 China

Funding

National Key Research and Development Program of China

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