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Biology
Special Issues
Genetic and Epigenetic Regulation of Gene Expression
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Genetic and Epigenetic Regulation of Gene Expression

A special issue of Biology (ISSN 2079-7737). This special issue belongs to the section "Genetics and Genomics".

Deadline for manuscript submissions: 31 January 2027 | Viewed by 9249

Special Issue Editor

Dr. Xu Wang

E-Mail Website
Guest Editor
Department of Pathobiology, College of Veterinary Medicine, Auburn University, Auburn, AL 36849, USA
Interests: agricultural genomics; allelic imbalance; DNA methylation; genomic imprinting
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

This Special Issue explores the mechanisms controlling when, where, and how genes are expressed to shape cellular and organismal functions. The genetic regulation of gene expression includes DNA sequences, such as promoters, enhancers, insulators, and small RNA target sequences, as well as cis-regulatory polymorphisms within them, that modulate transcriptional activity and transcript stability as well as maturation. It also involves a combination of transcription factors, cofactors, and RNA-binding proteins interacting with these sequences to modulate gene activity. In parallel, epigenetic mechanisms affect gene expression through modifications, such as chromatin remodeling, DNA methylation, histone modifications, and the activities of non-coding RNAs. These epigenetic changes are essential for developmental differentiation, responses to environmental stimuli, and the maintenance of genome stability. Furthermore, they can be heritable, reprogrammable, and reversible, providing an additional layer of regulatory complexity. Advances in technologies, like next-generation sequencing, single-cell genomics, and epigenomic profiling, have significantly deepened our understanding of these regulatory systems. This Special Issue aims to elucidate further the molecular, cellular, and systemic principles underlying the genetic and epigenetic regulation of gene expression, with potential applications in agricultural genomics, personalized medicine, and biotechnology.

Dr. Xu Wang
Guest Editor

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Keywords

  • allele-specific expression
  • cis-regulatory elements
  • RNA maturation and stability
  • DNA methylation
  • histone modifications
  • chromatin remodeling
  • transcription factors
  • non-coding RNA
  • small RNA

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Published Papers (6 papers)

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Research

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11 pages, 1616 KB  
Article
Identification and Analysis of Key lncRNAs for Adipose Differentiation
by Xiujie Xie, Tianyu Li, Bohang Zhang, Junxiong Liao, Xing Zhang, Jing Gao, Xiaofang Cheng, Tiantian Meng, Yongjie Xu, Pengpeng Zhang and Cencen Li
Biology 2026, 15(1), 87; https://doi.org/10.3390/biology15010087 - 31 Dec 2025
Viewed by 591
Abstract
Recent studies have demonstrated that the abundance of brown adipose tissue is inversely associated with obesity in humans. Promoting the browning of white adipocytes therefore represents a promising therapeutic strategy for obesity treatment. LncRNAs are known regulators of adipocyte differentiation and metabolic processes. [...] Read more.
Recent studies have demonstrated that the abundance of brown adipose tissue is inversely associated with obesity in humans. Promoting the browning of white adipocytes therefore represents a promising therapeutic strategy for obesity treatment. LncRNAs are known regulators of adipocyte differentiation and metabolic processes. However, their specific roles in adipocyte browning remain poorly characterized. In this study, we performed transcriptomic analyses using publicly available RNA-seq datasets of mouse white, brown and beige adipose tissues from the EMBL-EBI database. Our analytical workflow included raw data quality control, alignment to the reference genome, transcript assembly, coding potential assessment and differential expression analysis. Functional annotation was conducted through Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. Key lncRNAs were further validated via Reverse Transcription Quantitative PCR (RT-qPCR). We identified 794 novel lncRNAs and 1499 DEGs, among which 95 were common across all three adipocyte types. Two lncRNAs, MSTRG.12661 and MSTRG.17758, were found to be closely related to critical biological processes, including extracellular matrix organization and fatty acid oxidation. Functional prediction suggests their potential involvement in adipocyte type-specific differentiation. In conclusion, our study reveals novel lncRNAs that may regulate adipocyte differentiation, offering new candidate targets for obesity treatment via induction of white adipose tissue browning. Full article
(This article belongs to the Special Issue Genetic and Epigenetic Regulation of Gene Expression)
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14 pages, 8254 KB  
Article
DNA Methylation of Igf2r Promoter CpG Island 2 Governs Cis-Acting Inheritance and Gene Dosage in Equine Hybrids
by Xisheng Wang, Yingchao Shen, Hong Ren, Minna Yi and Gerelchimeg Bou
Biology 2025, 14(6), 678; https://doi.org/10.3390/biology14060678 - 11 Jun 2025
Viewed by 1562
Abstract
Genomic imprinting is critical for mammalian development, but its regulation varies across species. The insulin-like growth factor 2 receptor (IGF2R), which is a maternally expressed imprinted gene critical for cell proliferation and differentiation, as well as embryonic and placental development, is classically regulated [...] Read more.
Genomic imprinting is critical for mammalian development, but its regulation varies across species. The insulin-like growth factor 2 receptor (IGF2R), which is a maternally expressed imprinted gene critical for cell proliferation and differentiation, as well as embryonic and placental development, is classically regulated by differentially methylated regions (DMRs) and lncRNA-Airn in mice. However, studies on this in equus are scarce, especially in terms of mechanistic studies. In the present study, heart, liver, spleen, lung, kidney, brain, and muscle samples were obtained from horses, donkeys, and hybrids, and gene expression and imprinting state were tested to investigate the imprinting regulation of Igf2r in these animals. Bisulfite sequencing combined with an allele-specific expression analysis revealed a tissue-specific loss of imprinting in the mule liver and hybrid brain tissues. Strikingly, we found that the maternal-specific expression of equine Igf2r did not rely on the canonical DMRs or lncRNA-Airn. Surprisingly, DNA methylation of a specific region called CpG island 2 (CpGI2) in the Igf2r promoter showed cis-acting inheritance, meaning that the DNA methylation patterns of the parental alleles are retained in hybrid tissues. Notably, the DNA methylation of CpGI2 correlated negatively with Igf2r expression in the spleen (R2 = 0.8797, p = 6.46 × 10−6), lung (R2 = 0.8569, p = 1.57 × 10−5), and kidney (R2 = 0.8650, p = 3.85 × 10−6). Our findings suggest that imprinting may work differently in other species. This study provides a framework for understanding imprinting diversity in hybrids and shows that equine hybrids can be used to study how epigenetic inheritance works. Full article
(This article belongs to the Special Issue Genetic and Epigenetic Regulation of Gene Expression)
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Review

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22 pages, 972 KB  
Review
DNMT/TET Imbalance and Network-Level DNA Methylation Remodeling in Ovarian Aging: Mechanistic Perspectives
by Miaofang Lin, Sheng Yang, Fengwen Huang, Xiaoyifan Deng, Chengwan Shen, Xiangkai Zhen and Aikebaier Reheman
Biology 2026, 15(7), 577; https://doi.org/10.3390/biology15070577 - 3 Apr 2026
Viewed by 823
Abstract
Reproductive aging is characterized by progressive decline in ovarian reserve, reduced oocyte competence, and impaired endocrine coordination. Although these phenotypic changes are well documented, the molecular mechanisms that integrate aging-associated stress signals into coordinated ovarian dysfunction remain incompletely understood. Increasing evidence indicates that [...] Read more.
Reproductive aging is characterized by progressive decline in ovarian reserve, reduced oocyte competence, and impaired endocrine coordination. Although these phenotypic changes are well documented, the molecular mechanisms that integrate aging-associated stress signals into coordinated ovarian dysfunction remain incompletely understood. Increasing evidence indicates that DNA methylation remodeling is closely associated with ovarian aging. Rather than representing isolated promoter-specific events, age-related methylation alterations may reflect progressive imbalance between DNA methyltransferases (DNMTs) and TET-mediated demethylation. Stress-responsive DNMT/TET dysregulation has been linked to distributed epigenetic remodeling across regulatory elements governing PI3K–AKT, TGF-β/SMAD, metabolic, and DNA damage response pathways in ovarian cell populations. We propose a network-level framework in which methylation drift preferentially affects highly connected regulatory hubs, potentially reducing transcriptional robustness and intercellular coordination within the follicular microenvironment. However, current human data remain largely correlative, and functional validation is required to determine whether methylation remodeling acts as a driver, amplifier, or biomarker of ovarian aging. Finally, we discuss translational implications, including circulating cell-free DNA signatures and epigenetic clock models, while emphasizing the importance of cell type-resolved and longitudinal studies. Collectively, the available evidence supports a model in which progressive DNMT/TET imbalance is associated with distributed pathway-level regulatory instability during ovarian aging. Full article
(This article belongs to the Special Issue Genetic and Epigenetic Regulation of Gene Expression)
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30 pages, 3618 KB  
Review
The Structure, Classification, Functional Diversity and Regulatory Mechanism of Plant C2H2 Transcription Factors
by Junbai Ma, Xinyi Zhang, Shan Jiang, Shuoyao Fei, Lingyang Kong, Meitong Pan, Wei Ma and Weichao Ren
Biology 2026, 15(6), 471; https://doi.org/10.3390/biology15060471 - 14 Mar 2026
Viewed by 797
Abstract
Cys2/His2-type zinc finger transcription factors (C2H2 TFs) constitute one of the largest and most functionally diverse transcription factor families in plants, playing core regulatory roles in multiple aspects of plant growth, development, and stress adaptation. Based on literature data from databases including PubMed [...] Read more.
Cys2/His2-type zinc finger transcription factors (C2H2 TFs) constitute one of the largest and most functionally diverse transcription factor families in plants, playing core regulatory roles in multiple aspects of plant growth, development, and stress adaptation. Based on literature data from databases including PubMed (1995–April 2026) and integrated with bioinformatics analyses, this review provides a comprehensive overview of this family. We first summarize the structural characteristics and classification systems of C2H2 TFs, and elucidate their evolutionary dynamics from lower plants to angiosperms. Regarding their impact on plant organ development, beyond key biological processes, this review details the molecular mechanisms of C2H2 TFs in floral organ morphogenesis (e.g., petal, sepal, stamen, and ovule development), pollen fertility maintenance, and flowering time regulation. Concurrently, we systematically analyze their functional pathways in responses to abiotic stresses (drought, high salinity, low temperature, aluminum toxicity, etc.) and biotic stresses (pathogens, pests), clarifying the molecular networks through which they coordinate reactive oxygen species (ROS) homeostasis, stomatal movement, and osmotic regulation by modulating hormone signaling pathways such as ABA, SA, and JA. Furthermore, this review discusses major limitations of current research, including knowledge gaps concerning functional redundancy, pseudogenization phenomena, and cell type-specific regulation. We also provide perspectives on future research directions leveraging cutting-edge technologies such as CRISPR gene editing, single-cell sequencing, and multi-omics integration, as well as their application prospects in crop stress resistance breeding and quality improvement. This review provides ideas for in-depth research on the regulatory network and related functions of C2H2 TFs, and offers reference value for improving plant traits, enhancing plant resistance, and increasing the production of plant secondary metabolites. Full article
(This article belongs to the Special Issue Genetic and Epigenetic Regulation of Gene Expression)
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20 pages, 1085 KB  
Review
Evolution and Comparative Analysis of Sheep Reference Genomes: From Fragmented Assemblies to Telomere-to-Telomere Genomics
by Dan Yue, Ying Lu, Yuqing Chong, Jiao Wu, Zhendong Gao, Ruoshan Ma, Keyu Li, Weidong Deng and Bo Wang
Biology 2026, 15(6), 465; https://doi.org/10.3390/biology15060465 - 13 Mar 2026
Viewed by 680
Abstract
The reference genome serves as a fundamental resource for sheep genetic research and molecular breeding, and iterative improvements in assembly quality have directly driven advances in these fields. A systematic literature review was conducted by retrieving relevant studies from major scientific databases using [...] Read more.
The reference genome serves as a fundamental resource for sheep genetic research and molecular breeding, and iterative improvements in assembly quality have directly driven advances in these fields. A systematic literature review was conducted by retrieving relevant studies from major scientific databases using predefined keywords related to sheep reference genomes and genome assembly technologies, followed by structured screening and comparative analysis of eligible publications. This review systematically summarizes the developmental trajectory of the sheep reference genome from early fragmented assemblies to telomere-to-telomere (T2T) genome assembly approaches. Different genome versions are comparatively analyzed from multiple perspectives, including assembly strategies, quality metrics, and functional annotation. Importantly, we propose a genome-resolution-driven analytical framework that explicitly links successive improvements in reference genome completeness with paradigm shifts in sheep genetic analysis, ranging from marker-based studies to structural variation- and multi-omics-enabled trait dissection. Particular emphasis is placed on the potential applications and biological research value of T2T genomes in assembly methodologies and multi-omics integrative analyses. Furthermore, the practical significance of different reference genome versions in genetic dissection, trait mapping, and breeding applications is reviewed, and future directions for sheep genome research are discussed. This review provides both a systematic synthesis and a forward-looking conceptual roadmap for advancing sheep molecular genetics and precision breeding in the T2T genomics era. Full article
(This article belongs to the Special Issue Genetic and Epigenetic Regulation of Gene Expression)
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22 pages, 1455 KB  
Review
Cross-Kingdom DNA Methylation Dynamics: Comparative Mechanisms of 5mC/6mA Regulation and Their Implications in Epigenetic Disorders
by Yu Liu, Ying Wang, Dapeng Bao, Hongyu Chen, Ming Gong, Shujing Sun and Gen Zou
Biology 2025, 14(5), 461; https://doi.org/10.3390/biology14050461 - 24 Apr 2025
Cited by 5 | Viewed by 3555
Abstract
DNA methylation, a cornerstone of epigenetic regulation, governs critical biological processes including transcriptional modulation, genomic imprinting, and transposon suppression through chromatin architecture remodeling. Recent advances have revealed that aberrant methylation patterns—characterized by spatial-temporal dysregulation and stochastic molecular noise—serve as key drivers of diverse [...] Read more.
DNA methylation, a cornerstone of epigenetic regulation, governs critical biological processes including transcriptional modulation, genomic imprinting, and transposon suppression through chromatin architecture remodeling. Recent advances have revealed that aberrant methylation patterns—characterized by spatial-temporal dysregulation and stochastic molecular noise—serve as key drivers of diverse pathological conditions, from oncogenesis to neurodegenerative disorders. However, the field faces dual challenges: (1) current understanding remains fragmented due to the inherent spatiotemporal heterogeneity of methylation landscapes across tissues and developmental stages, and (2) mechanistic insights into non-canonical methylation pathways (particularly 6mA) in non-mammalian systems are conspicuously underdeveloped. This review systematically synthesizes the evolutionary-conserved versus species-specific features of 5-methylcytosine (5mC) and N6-methyladenine (6mA) regulatory networks across three biological kingdoms. Through comparative analysis of methylation/demethylation enzymatic cascades (DNMTs/TETs in mammals, CMTs/ROS1 in plants, and DIM-2/DNMTA in fungi), we propose a unified framework for targeting methylation-associated diseases through precision epigenome editing, while identifying critical knowledge gaps in fungal methylome engineering that demand urgent investigation. Full article
(This article belongs to the Special Issue Genetic and Epigenetic Regulation of Gene Expression)
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