Journal of Genetics and Genomics

The future of zebrafish research: highlights from the 18th International Zebrafish Conference

Chenyang Bian, Dongyuan Ma, Feng Liu

2025, 52(1): 1-3. doi: 10.1016/j.jgg.2024.09.006

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Crop root system architecture in drought response

Yanjun Zhang, Xi Wu, Xingrong Wang, Mingqiu Dai, Yunling Peng

2025, 52(1): 4-13. doi: 10.1016/j.jgg.2024.05.001

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Drought is a natural disaster that profoundly impacts on global agricultural production, significantly reduces crop yields, and thereby poses a severe threat to worldwide food security. Addressing the challenge of effectively improving crop drought resistance (DR) to mitigate yield loss under drought conditions is a global issue. An optimal root system architecture (RSA) plays a pivotal role in enhancing the capacity of crops to efficiently uptake water and nutrients, which consequently strengthens their resilience against environmental stresses. In this review, we discuss the compositions and roles of crop RSA and summarize the most recent developments in augmenting drought tolerance in crops by manipulating RSA-related genes. Based on the current research, we propose the potential optimal RSA configuration that could be helpful in enhancing crop DR. Lastly, we discuss the existing challenges and future directions for breeding crops with enhanced DR capabilities through genetic improvements targeting RSA.

The interplay between extracellular and intracellular auxin signaling in plants

Wenxin Tang, Yongqiang Yu, Tongda Xu

2025, 52(1): 14-23. doi: 10.1016/j.jgg.2024.06.019

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The phytohormone auxin exerts control over remarkable developmental processes in plants. It moves from cell to cell, resulting in the creation of both extracellular auxin and intracellular auxin, which are recognized by distinct auxin receptors. These two auxin signaling systems govern different auxin responses while working together to regulate plant development. In this review, we outline the latest research advancements in unraveling these auxin signaling pathways, encompassing auxin perception and signaling transductions. We emphasize the interaction between extracellular and intracellular auxin, which contributes to the intricate role of auxin in plant development.

The interplay between histone modifications and nuclear lamina in genome regulation

Chang Sun, Yanjing Zhao, Liping Guo, Juhui Qiu, Qin Peng

2025, 52(1): 24-38. doi: 10.1016/j.jgg.2024.10.005

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Gene expression is regulated by chromatin architecture and epigenetic remodeling in cell homeostasis and pathologies. Histone modifications act as the key factors to modulate the chromatin accessibility. Different histone modifications are strongly associated with the localization of chromatin. Heterochromatin primarily localizes at the nuclear periphery, where it interacts with lamina proteins to suppress gene expression. In this review, we summarize the potential bridges that have regulatory functions of histone modifications in chromatin organization and transcriptional regulation at the nuclear periphery. We use lamina-associated domains (LADs) as examples to elucidate the biological roles of the interactions between histone modifications and nuclear lamina in cell differentiation and development. In the end, we highlight the technologies that are currently used to identify and visualize histone modifications and LADs, which could provide spatiotemporal information for understanding their regulatory functions in gene expression and discovering new targets for diseases.

KDM2A and KDM2B protect a subset of CpG islands from DNA methylation

Yuan Liu, Ying Liu, Yunji Zhu, Di Hu, Hu Nie, Yali Xie, Rongrong Sun, Jin He, Honglian Zhang, Falong Lu

2025, 52(1): 39-50. doi: 10.1016/j.jgg.2024.10.012

Abstract (2)

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In the mammalian genome, most CpGs are methylated. However, CpGs within the CpG islands (CGIs) are largely unmethylated, which are important for gene expression regulation. The mechanism underlying the low methylation levels at CGIs remains largely elusive. KDM2 proteins (KDM2A and KDM2B) are H3K36me2 demethylases known to bind specifically at CGIs. Here, we report that depletion of each or both KDM2 proteins, or mutation of all their JmjC domains that harbor the H3K36me2 demethylation activity, leads to an increase in DNA methylation at selective CGIs. The Kdm2a/2b double knockout shows a stronger increase in DNA methylation compared with the single mutant of Kdm2a or Kdm2b, indicating that KDM2A and KDM2B redundantly regulate DNA methylation at CGIs. In addition, the increase of CGI DNA methylation upon mutations of KDM2 proteins is associated with the chromatin environment. Our findings reveal that KDM2A and KDM2B function redundantly in regulating DNA methylation at a subset of CGIs in an H3K36me2 demethylation-dependent manner.

Rab1 and Syntaxin 17 regulate hematopoietic homeostasis through β-integrin trafficking in Drosophila

Fangzhou Luo, Luwei Sui, Ying Sun, Zhixian Lai, Chengcheng Zhang, Gaoqun Zhang, Bing Bi, Shichao Yu, Li Hua Jin

2025, 52(1): 51-65. doi: 10.1016/j.jgg.2024.11.001

Abstract (2)

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Hematopoiesis is crucial for organismal health, and Drosophila serves as an effective genetic model due to conserved regulatory mechanisms with vertebrates. In larvae, hematopoiesis primarily occurs in the lymph gland, which contains distinct zones, including the cortical zone, intermediate zone, medullary zone, and posterior signaling center (PSC). Rab1 is vital for membrane trafficking and maintaining the localization of cell adhesion molecules, yet its role in hematopoietic homeostasis is not fully understood. This study investigates the effects of Rab1 dysfunction on β-integrin trafficking within circulating hemocytes and lymph gland cells. Rab1 impairment disrupts the endosomal trafficking of β-integrin, leading to its abnormal localization on cell membranes, which promotes lamellocyte differentiation and alters progenitor dynamics in circulating hemocytes and lymph glands, respectively. We also show that the mislocalization of β-integrin is dependent on the adhesion protein DE-cadherin. The reduction of β-integrin at cell boundaries in PSC cells leads to fewer PSC cells and lamellocyte differentiation. Furthermore, Rab1 regulates the trafficking of β-integrin via the Q-SNARE protein Syntaxin 17 (Syx17). Our findings indicate that Rab1 and Syx17 regulate distinct trafficking pathways for β-integrin in different hematopoietic compartments and maintain hematopoietic homeostasis of Drosophila.

Prox1a promotes liver growth and differentiation by repressing cdx1b expression and intestinal fate transition in zebrafish

Yingying Hu, Zhou Luo, Meiwen Wang, Zekai Wu, Yunxing Liu, Zhenchao Cheng, Yuhan Sun, Jing-Wei Xiong, Xiangjun Tong, Zuoyan Zhu, Bo Zhang

2025, 52(1): 66-77. doi: 10.1016/j.jgg.2024.09.010

Abstract (2)

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The liver is a key endoderm-derived multifunctional organ within the digestive system. Prospero homeobox 1 (Prox1) is an essential transcription factor for liver development, but its specific function is not well understood. Here, we show that hepatic development, including the formation of intrahepatic biliary and vascular networks, is severely disrupted in prox1a mutant zebrafish. We find that Prox1a is essential for liver growth and proper differentiation but not required for early hepatic cell fate specification. Intriguingly, prox1a depletion leads to ectopic initiation of a Cdx1b-mediated intestinal program and the formation of intestinal lumen-like structures within the liver. Morpholino knockdown of cdx1b alleviates liver defects in the prox1a mutant zebrafish. Finally, chromatin immunoprecipitation analysis reveals that Prox1a binds directly to the promoter region of cdx1b, thereby repressing its expression. Overall, our findings indicate that Prox1a is required to promote and protect hepatic development by repression of Cdx1b-mediated intestinal cell fate in zebrafish.

Epigenetic basis for the establishment of ruminal tissue-specific functions in bovine fetuses and adults

Jing Wang, Wen Yuan, Fang Liu, Guangbo Liu, Xiaoxiong Geng, Chen Li, Chenchen Zhang, Nan Li, Xueling Li

2025, 52(1): 78-92. doi: 10.1016/j.jgg.2024.10.008

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Epigenetic regulation in the rumen, a unique ruminant organ, remains largely unexplored compared with other tissues studied in model species. In this study, we perform an in-depth analysis of the epigenetic and transcriptional landscapes across fetal and adult bovine tissues as well as pluripotent stem cells. Among the extensive methylation differences across various stages and tissues, we identify tissue-specific differentially methylated regions (tsDMRs) unique to the rumen, which are crucial for regulating epithelial development and energy metabolism. These tsDMRs cluster within super-enhancer regions that overlap with transcription factor (TF) binding sites. Regression models indicate that DNA methylation, along with H3K27me3 and H3K27ac, can be used to predict enhancer activity. Key upstream TFs, including SOX2, FOSL1/2, and SMAD2/3, primarily maintain an inhibitory state through bivalent modifications during fetal development. Downstream functional genes are maintained mainly in a stable repressive state via DNA methylation until differentiation is complete. Our study underscores the critical role of tsDMRs in regulating distal components of rumen morphology and function, providing key insights into the epigenetic regulatory mechanisms that may influence bovine production traits.

SpaGRA: Graph augmentation facilitates domain identification for spatially resolved transcriptomics

Xue Sun, Wei Zhang, Wenrui Li, Na Yu, Daoliang Zhang, Qi Zou, Qiongye Dong, Xianglin Zhang, Zhiping Liu, Zhiyuan Yuan, Rui Gao

2025, 52(1): 93-104. doi: 10.1016/j.jgg.2024.09.015

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Recent advances in spatially resolved transcriptomics (SRT) have provided new opportunities for characterizing spatial structures of various tissues. Graph-based geometric deep learning has gained widespread adoption for spatial domain identification tasks. Currently, most methods define adjacency relation between cells or spots by their spatial distance in SRT data, which overlooks key biological interactions like gene expression similarities, and leads to inaccuracies in spatial domain identification. To tackle this challenge, we propose a novel method, SpaGRA (https://github.com/sunxue-yy/SpaGRA), for automatic multi-relationship construction based on graph augmentation. SpaGRA uses spatial distance as prior knowledge and dynamically adjusts edge weights with multi-head graph attention networks (GATs). This helps SpaGRA to uncover diverse node relationships and enhance message passing in geometric contrastive learning. Additionally, SpaGRA uses these multi-view relationships to construct negative samples, addressing sampling bias posed by random selection. Experimental results show that SpaGRA presents superior domain identification performance on multiple datasets generated from different protocols. Using SpaGRA, we analyze the functional regions in the mouse hypothalamus, identify key genes related to heart development in mouse embryos, and observe cancer-associated fibroblasts enveloping cancer cells in the latest Visium HD data. Overall, SpaGRA can effectively characterize spatial structures across diverse SRT datasets.

Improving precision base editing of the zebrafish genome by Rad51DBD-incorporated single-base editors

Zhilin Zhong, Xueli Hu, Renjie Zhang, Xu Liu, Wenqi Chen, Shubin Zhang, Jianjian Sun, Tao P. Zhong

2025, 52(1): 105-115. doi: 10.1016/j.jgg.2024.10.006

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Single-base editors, including cytosine base editors (CBEs) and adenine base editors (ABEs), facilitate accurate C·G to T·A and A·T to G·C, respectively, holding promise for the precise modeling and treatment of human hereditary disorders. Efficient base editing and expanded base conversion range have been achieved in human cells through base editors fusing with Rad51 DNA binding domain (Rad51DBD), such as hyA3A-BE4max. Here, we show that hyA3A-BE4max catalyzes C-to-T substitution in the zebrafish genome and extends editing positions (C₁₂–C₁₆) proximal to the protospacer adjacent motif. We develop a codon-optimized counterpart zhyA3A-CBE5, which exhibits substantially high C-to-T conversion with 1.59- to 3.50-fold improvement compared with the original hyA3A-BE4max. With these tools, disease-relevant hereditary mutations can be more efficaciously generated in zebrafish. We introduce human genetic mutation rpl11^Q42∗ and abcc6a^R1463C by zhyA3A-CBE5 in zebrafish, mirroring Diamond-Blackfan anemia and Pseudoxanthoma Elasticum, respectively. Our study expands the base editing platform targeting the zebrafish genomic landscape and the application of single-base editors for disease modeling and gene function study.

Pan-genome analyses add ∼1000 genes to the “complete” genome assembly of chicken

Jilong Ren, Wenyan Kou, Yuan Xu, Meixuan Lu, Mian Gong, Xinmiao Zhang, Zhenyu Liu, Hengkuan Li, Qimeng Yang, Ali Mujtaba Shah, Feng Zhu, Zhuocheng Hou, Naiyi Xu, Yu Jiang, Fei Wang

2025, 52(1): 116-119. doi: 10.1016/j.jgg.2024.10.009

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TaNPF6.2 improves agronomic traits via enhancing nitrogen uptake efficiency in wheat

Huanhuan Wang, Yangyang Liu, Lifen Wu, Chuan Xia, Yaoyu Chen, Xiuying Kong, Feng Shi, Huili Li, Xifang Yang, Liang Ma, Jiaqiang Sun, Lichao Zhang, Zhencheng Xie

2025, 52(1): 120-123. doi: 10.1016/j.jgg.2024.11.004

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Zebrafish cartilage development atlas generated by longitudinal in vivo imaging

Shirong Jin, Hongfei Zhang, Jia Li, Huaxing Zi, Jiulin Du, Hongyu Li

2025, 52(1): 124-127. doi: 10.1016/j.jgg.2024.11.003

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2025 Vol. 52, No. 1