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16 pages, 876 KiB  
Article
M72 Fusion Proteins in Nanocapsules Enhance BCG Efficacy Against Bovine Tuberculosis in a Mouse Model
by Federico Carlos Blanco, Renée Onnainty, María Rocío Marini, Laura Inés Klepp, Elizabeth Andrea García, Cristina Lourdes Vazquez, Ana Canal, Gladys Granero and Fabiana Bigi
Pathogens 2025, 14(6), 592; https://doi.org/10.3390/pathogens14060592 - 16 Jun 2025
Viewed by 522
Abstract
Mycobacterium bovis is the causative pathogen of bovine tuberculosis (bTB), a disease that affects cattle and other mammals, including humans. Currently, there is no efficient vaccine against bTB, underscoring the need for novel immunization strategies. The M72 fusion protein, composed of three polypeptides derived [...] Read more.
Mycobacterium bovis is the causative pathogen of bovine tuberculosis (bTB), a disease that affects cattle and other mammals, including humans. Currently, there is no efficient vaccine against bTB, underscoring the need for novel immunization strategies. The M72 fusion protein, composed of three polypeptides derived from Mycobacterium tuberculosis and M. bovis, has demonstrated protective efficacy against M. tuberculosis in clinical trials when combined with the AS01E adjuvant. Given the established efficacy of nanocapsule formulations as vaccine delivery systems, this study evaluated a novel immunization strategy combining BCG with either full-length M72 or a truncated M72 fused to a streptococcal albumin-binding domain (ABDsM72). Both antigens were encapsulated in chitosan/alginate nanocapsules and assessed in a murine M. bovis challenge model. Priming with BCG followed by an M72 boost significantly improved splenic protection compared to BCG alone, but it did not enhance pulmonary protection. Notably, boosting with ABDsM72 further increased the proportion of CD4+KLRG1-CXCR3+ T cells in the lungs of M. bovis-challenged mice, a key correlate of protective immunity. These findings demonstrate that chitosan/alginate-encapsulated antigens enhance BCG-induced immunity, supporting their potential as next-generation vaccine candidates for bTB control. Full article
(This article belongs to the Special Issue Mycobacterial Infection: Pathogenesis and Drug Development)
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21 pages, 3971 KiB  
Article
Genome-Wide Identification of the BTB Domain-Containing Protein Gene Family in Pepper (Capsicum annuum L.)
by Qiaoling Yuan, Jin Wang, Feng Liu, Xiongze Dai, Fan Zhu, Xuexiao Zou and Cheng Xiong
Int. J. Mol. Sci. 2025, 26(7), 3429; https://doi.org/10.3390/ijms26073429 - 6 Apr 2025
Viewed by 667
Abstract
Pepper (Capsicum annuum L.), recognized as a globally preeminent vegetable, holds substantial economic and nutritional value. The BTB (broad-complex, tramtrack, and bric-a-brac) family of proteins, characterized by a highly conserved BTB domain, also denoted as the POZ domain, are intricately involved in [...] Read more.
Pepper (Capsicum annuum L.), recognized as a globally preeminent vegetable, holds substantial economic and nutritional value. The BTB (broad-complex, tramtrack, and bric-a-brac) family of proteins, characterized by a highly conserved BTB domain, also denoted as the POZ domain, are intricately involved in a diverse array of biological processes. However, the existing corpus of research regarding pepper BTB genes remains relatively meager. In this study, a total of 72 CaBTB gene members were meticulously identified from the entire genome of pepper. Phylogenetic analysis illuminated the presence of conspicuous collinear relationships between the CaBTB genes and those of its closely affiliated species. Gene expression profiling and RT-qPCR analysis revealed that multiple CaBTB genes exhibited pronounced differential expression under diverse treatment regimens. Expression pattern analysis unveiled that CaBTB25 manifested a remarkably elevated abundance in leaves. Moreover, its promoters were replete with an abundance of light-responsive cis-elements. Our comprehensive and in-depth explorations into subcellular localization revealed that CaBTB25 was predominantly detected to localize within the nucleus and lacked transcriptional activation. This research provides a crucial theoretical edifice, enabling a more profound understanding of the biological functions of the BTB gene family in pepper, thereby underscoring its potential significance within the intricate network of gene–environment interactions. Full article
(This article belongs to the Special Issue Plant Responses to Abiotic and Biotic Stresses)
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20 pages, 10010 KiB  
Article
Genome-Wide Analysis of NPH3/RPT2-like (NRL) Genes in Grape (Vitis vinifera L.): Their Identification, Characterization, and Different Responses to Light Quality
by Shiyang Li, Hongsheng Gao, Xiaoyan Li, Yihua Liu, Hang Zhao, Nianwei Qiu and Hongxia Zhang
Horticulturae 2025, 11(3), 274; https://doi.org/10.3390/horticulturae11030274 - 3 Mar 2025
Viewed by 694
Abstract
NRL (NPH3/RPT2-Like) proteins, which are exclusive to plants, serve as critical mediators in phototropic signaling by dynamically regulating light-dependent cellular processes. We identified 24 NRL genes (VvNRL) in the Vitis vinifera L. genome, which were unevenly distributed on 11 chromosomes. Phylogenetic analysis [...] Read more.
NRL (NPH3/RPT2-Like) proteins, which are exclusive to plants, serve as critical mediators in phototropic signaling by dynamically regulating light-dependent cellular processes. We identified 24 NRL genes (VvNRL) in the Vitis vinifera L. genome, which were unevenly distributed on 11 chromosomes. Phylogenetic analysis showed that these family members were divided into six groups, and promoter analysis revealed ubiquitous light-responsive cis-elements across all 24 members, suggesting conserved regulatory mechanisms. Sequence alignment and structural similarity analysis showed that VvNRL4 and VvNRL6 were highly similar to NPH3 and NPR2. Experiments with different light qualities showed that VvNRL6 was induced by blue and red light, while VvNRL4 was not affected by light spectra, similar to NPH3 in Arabidopsis. Molecular docking prediction suggested that VvNRL4 and VvNRL6 may, respectively, interact with the LOV domain in VvPHO1 and VvPHO2, through their C-terminal coiled-coil domain and N-terminal BTB domain, to further regulate the activity of VvPHO1 and VvPHO2. In addition, 10 of the 24 VvNRLs, including VvNRL4 and VvNRL6, possessed the conserved RxS motif in their conserved C-terminal consensus sequences. This study provides a reference for further studies on the function and regulation of VvNRL family members in fruit vine plants. Full article
(This article belongs to the Section Genetics, Genomics, Breeding, and Biotechnology (G2B2))
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13 pages, 2543 KiB  
Article
Comprehensive Annotation and Expression Profiling of C2H2 Zinc Finger Transcription Factors across Chicken Tissues
by Shuai Chen, Jiayao Jiang, Wenxiu Liang, Yuchen Tang, Renzhe Lyu, Yun Hu, Demin Cai, Xugang Luo and Mingan Sun
Int. J. Mol. Sci. 2024, 25(19), 10525; https://doi.org/10.3390/ijms251910525 - 30 Sep 2024
Viewed by 1173
Abstract
As the most abundant class of transcription factors in eukaryotes, C2H2-type zinc finger proteins (C2H2-ZFPs) play critical roles in various biological processes. Despite being extensively studied in mammals, C2H2-ZFPs remain poorly characterized in birds. Recent accumulation of multi-omics data for chicken enables the [...] Read more.
As the most abundant class of transcription factors in eukaryotes, C2H2-type zinc finger proteins (C2H2-ZFPs) play critical roles in various biological processes. Despite being extensively studied in mammals, C2H2-ZFPs remain poorly characterized in birds. Recent accumulation of multi-omics data for chicken enables the genome-wide investigation of C2H2-ZFPs in birds. The purpose of this study is to reveal the genomic occurrence and evolutionary signature of chicken C2H2-ZFPs, and further depict their expression profiles across diverse chicken tissues. Here, we annotated 301 C2H2-ZFPs in chicken genome, which are associated with different effector domains, including KRAB, BTB, HOMEO, PHD, SCAN, and SET. Among them, most KRAB-ZFPs lack orthologues in mammals and tend to form clusters by duplication, supporting their fast evolution in chicken. We also annotated a unique and previously unidentified SCAN-ZFP, which is lineage-specific and highly expressed in ovary and testis. By integrating 101 RNA-seq datasets for 32 tissues, we found that most C2H2-ZFPs have tissue-specific expression. Particularly, 74 C2H2-ZFPs—including 27 KRAB-ZFPs—show blastoderm-enriched expression, indicating their association with early embryo development. Overall, this study performs comprehensive annotation and expression profiling of C2H2 ZFPs in diverse chicken tissues, which gives new insights into the evolution and potential function of C2H2-ZFPs in avian species. Full article
(This article belongs to the Special Issue Molecular Research in Avian Genetics)
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18 pages, 8138 KiB  
Article
Genome-Wide Characterization of the BTB Gene Family in Poplar and Expression Analysis in Response to Hormones and Biotic/Abiotic Stresses
by Jing Yue, Xinren Dai, Quanzi Li and Mingke Wei
Int. J. Mol. Sci. 2024, 25(16), 9048; https://doi.org/10.3390/ijms25169048 - 21 Aug 2024
Cited by 3 | Viewed by 1643
Abstract
The BTB (Broad-complex, tramtrack, and bric-a-brac) gene family, characterized by a highly conserved BTB domain, is implicated in a spectrum of biological processes, encompassing growth and development, as well as stress responses. Characterization and functional studies of BTB genes in poplar are still [...] Read more.
The BTB (Broad-complex, tramtrack, and bric-a-brac) gene family, characterized by a highly conserved BTB domain, is implicated in a spectrum of biological processes, encompassing growth and development, as well as stress responses. Characterization and functional studies of BTB genes in poplar are still limited, especially regarding their response to hormones and biotic/abiotic stresses. In this study, we conducted an HMMER search in conjunction with BLASTp and identified 95 BTB gene models in Populus trichocarpa. Through domain motif and phylogenetic relationship analyses, these proteins were classified into eight families, NPH3, TAZ, Ankyrin, only BTB, BACK, Armadillo, TPR, and MATH. Collinearity analysis of poplar BTB genes with homologs in six other species elucidated evolutionary relationships and functional conservations. RNA-seq analysis of five tissues of poplar identified BTB genes as playing a pivotal role during developmental processes. Comprehensive RT-qPCR analysis of 11 BTB genes across leaves, roots, and xylem tissues revealed their responsive expression patterns under diverse hormonal and biotic/abiotic stress conditions, with varying degrees of regulation observed in the results. This study marks the first in-depth exploration of the BTB gene family in poplar, providing insights into the potential roles of BTB genes in hormonal regulation and response to stress. Full article
(This article belongs to the Section Molecular Genetics and Genomics)
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14 pages, 4607 KiB  
Article
Arabidopsis BTB-A2s Play a Key Role in Drought Stress
by Guohua Cai, Yunxiao Zang, Zhongqian Wang, Shuoshuo Liu and Guodong Wang
Biology 2024, 13(8), 561; https://doi.org/10.3390/biology13080561 - 26 Jul 2024
Cited by 3 | Viewed by 1474
Abstract
Drought stress significantly impacts plant growth, productivity, and yield, necessitating a swift fine-tuning of pathways for adaptation to harsh environmental conditions. This study explored the effects of Arabidopsis BTB-A2.1, BTB-A2.2, and BTB-A2.3, distinguished by their exclusive possession of the Broad-complex, Tramtrack, and Bric-à-brac [...] Read more.
Drought stress significantly impacts plant growth, productivity, and yield, necessitating a swift fine-tuning of pathways for adaptation to harsh environmental conditions. This study explored the effects of Arabidopsis BTB-A2.1, BTB-A2.2, and BTB-A2.3, distinguished by their exclusive possession of the Broad-complex, Tramtrack, and Bric-à-brac (BTB) domain, on the negative regulation of drought stress mediated by abscisic acid (ABA) signaling. Promoter analysis revealed the presence of numerous ABA-responsive and drought stress-related cis-acting elements within the promoters of AtBTB-A2.1, AtBTB-A2.2, and AtBTB-A2.3. The AtBTB-A2.1, AtBTB-A2.2, and AtBTB-A2.3 transcript abundances increased under drought and ABA induction according to qRT-PCR and GUS staining. Furthermore, the Arabidopsis btb-a2.1/2/3 triple mutant exhibited enhanced drought tolerance, supporting the findings from the overexpression studies. Additionally, we detected a decrease in the stomatal aperture and water loss rate of the Arabidopsis btb-a2.1/2/3 mutant, suggesting the involvement of these genes in repressing stomatal closure. Importantly, the ABA signaling-responsive gene levels within Arabidopsis btb-a2.1/2/3 significantly increased compared with those in the wild type (WT) under drought stress. Based on such findings, Arabidopsis BTB-A2s negatively regulate drought stress via the ABA signaling pathway. Full article
(This article belongs to the Section Biochemistry and Molecular Biology)
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17 pages, 2965 KiB  
Article
Gonadal Transcriptomic Analysis Reveals Novel Sex-Related Genes in Bactrocera dorsalis
by Qin Wang, Yuxuan Lei, Hongjie Lin, Xiaoxin Chen, Wanyu Mo, Boyang Guan and Huimin Deng
Insects 2024, 15(6), 424; https://doi.org/10.3390/insects15060424 - 5 Jun 2024
Viewed by 1406
Abstract
Bactrocera dorsalis (Hendel) (Diptera: Tephritidae) is one of the most devastating agricultural pests worldwide due to its high reproductive and invasive abilities. The elucidation of its gonadal developmental characteristics and the identification of sex-related genes will provide a useful genetic basis for reproductive-based [...] Read more.
Bactrocera dorsalis (Hendel) (Diptera: Tephritidae) is one of the most devastating agricultural pests worldwide due to its high reproductive and invasive abilities. The elucidation of its gonadal developmental characteristics and the identification of sex-related genes will provide a useful genetic basis for reproductive-based pest control. Here, the gonadal transcriptome of B. dorsalis was sequenced, and novel gonad-specific expressed genes were analyzed. A total of 1338, 336, 35, and 479 differentially expressed genes (DEGs) were found in the testis (TE), ovary (OV), female accessory gland (FAG), and male accessory gland (MAG), respectively. Furthermore, 463 highly expressed gonad-specific genes were identified, with the TE having the highest number of specific highly expressed genes, at 402, followed by 51 in the OV, 9 in the MAG, and only 1 in the FAG. Strikingly, approximately half of highly expressed gonad-specific genes were uncharacterized. Then, it was found that 35, 17, 3, 2, and 1 of 202 uncharacterized highly expressed TE-specific genes encoded proteins that contained transmembrane domains, signal peptides, high-mobility group boxes, the zinc finger domain, and the BTB/POZ domain, respectively. Interestingly, approximately 40% of uncharacterized highly expressed gonad-specific genes encoding proteins were not predicted to possess functional motifs or domains. Finally, the spatiotemporal expression and sequence characterization of six novel highly expressed gonad-specific genes were analyzed. Altogether, our findings provide a valuable dataset for future functional analyses of sex-related genes and potential target sites for pest control. Full article
(This article belongs to the Section Insect Molecular Biology and Genomics)
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14 pages, 14720 KiB  
Article
Identification and Expression Analysis of the BTB/POZ Gene Family in Solanum tuberosum
by Haoyue Feng, Yifei Lu, Bi Ren, Shimin Yang, Yongjian Liu, Liming Lu and Liqin Li
Horticulturae 2024, 10(6), 543; https://doi.org/10.3390/horticulturae10060543 - 23 May 2024
Cited by 2 | Viewed by 1618
Abstract
The BTB/POZ (broad-complex, tramtrack, and bric-a-brac) family of proteins is widespread in plants and animals and plays important roles in growth, development, metabolism, and environmental responses. There are few reports on BTB family genes in potato. In this study, 34 sequences containing conserved [...] Read more.
The BTB/POZ (broad-complex, tramtrack, and bric-a-brac) family of proteins is widespread in plants and animals and plays important roles in growth, development, metabolism, and environmental responses. There are few reports on BTB family genes in potato. In this study, 34 sequences containing conserved BTB domains were obtained from the potato gene database, and the phylogenetic, physical, and chemical properties, gene structure, conserved motif, domain, and chromosomal localization of the potato BTB protein family were analyzed via bioinformatics methods. In addition, we used qRT-PCR to detect 12 selected StBTB genes. The results confirmed that these genes are involved in cold, ABA, salt, hydrogen peroxide (H2O2), drought, and low-nitrogen stress, which is highly important for elucidating BTB family members and studying stress response and tolerance mechanisms. This study provides a theoretical basis for the study of the function and expression of potato BTB and lays a solid foundation for further understanding the molecular mechanism of the potato BTB gene under various environmental stresses. Full article
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16 pages, 2304 KiB  
Review
BACH2: The Future of Induced T-Regulatory Cell Therapies
by Daniel Zwick, Mai Tram Vo, Young Jun Shim, Helena Reijonen and Jeong-su Do
Cells 2024, 13(11), 891; https://doi.org/10.3390/cells13110891 - 22 May 2024
Cited by 3 | Viewed by 3998
Abstract
BACH2 (BTB Domain and CNC Homolog 2) is a transcription factor that serves as a central regulator of immune cell differentiation and function, particularly in T and B lymphocytes. A picture is emerging that BACH2 may function as a master regulator of cell [...] Read more.
BACH2 (BTB Domain and CNC Homolog 2) is a transcription factor that serves as a central regulator of immune cell differentiation and function, particularly in T and B lymphocytes. A picture is emerging that BACH2 may function as a master regulator of cell fate that is exquisitely sensitive to cell activation status. In particular, BACH2 plays a key role in stabilizing the phenotype and suppressive function of transforming growth factor-beta (TGF-β)-derived human forkhead box protein P3 (FOXP3)+ inducible regulatory T cells (iTregs), a cell type that holds great clinical potential as a cell therapeutic for diverse inflammatory conditions. As such, BACH2 potentially could be targeted to overcome the instability of the iTreg phenotype and suppressive function that has hampered their clinical application. In this review, we focus on the role of BACH2 in T cell fate and iTreg function and stability. We suggest approaches to modulate BACH2 function that may lead to more stable and efficacious Treg cell therapies. Full article
(This article belongs to the Section Cellular Immunology)
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23 pages, 6491 KiB  
Article
Genome-Wide Identification and Expression Analysis of the Broad-Complex, Tramtrack, and Bric-à-Brac Domain-Containing Protein Gene Family in Potato
by Aiana, Anita Katwal, Hanny Chauhan, Santosh Kumar Upadhyay and Kashmir Singh
Agriculture 2024, 14(5), 771; https://doi.org/10.3390/agriculture14050771 - 16 May 2024
Viewed by 2217
Abstract
The BTB (broad-complex, tramtrack, and bric-à-brac) domain, also known as the POZ (POX virus and zinc finger) domain, is a conserved protein–protein interaction domain present in various organisms. In this study, we conducted a genome-wide search to identify and characterize BTB genes in [...] Read more.
The BTB (broad-complex, tramtrack, and bric-à-brac) domain, also known as the POZ (POX virus and zinc finger) domain, is a conserved protein–protein interaction domain present in various organisms. In this study, we conducted a genome-wide search to identify and characterize BTB genes in Solanum tuberosum. A total of 57 StBTBs were identified and analyzed for their physicochemical properties, chromosomal distribution, gene structure, conserved motifs, phylogenetic relationships, tissue-specific expression patterns, and responses to hormonal and stress treatments. We found that StBTBs were unevenly distributed across potato chromosomes and exhibited diverse gene structures and conserved motifs. Tissue-specific expression analysis revealed differential expression patterns across various potato tissues, implying their roles in plant growth and development. Furthermore, differential expression analysis under hormonal and stress treatments indicated the involvement of StBTBs in abiotic and biotic stress responses and hormone signaling pathways. Protein–protein interaction analysis identified potential interactions with ribosomal proteins, suggesting roles in translational regulation. Additionally, microRNA target site analysis revealed regulatory relationships between StBTBs and miRNAs. Our study provides a comprehensive understanding of the StBTB gene family in potato, laying the groundwork for further functional characterization and manipulation of these genes to improve stress tolerance and agricultural productivity in potato and related plant species. Full article
(This article belongs to the Special Issue Abiotic Stress Responses in Horticultural Crops)
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15 pages, 4172 KiB  
Article
Identification and Functional Analysis of the fruitless Gene in a Hemimetabolous Insect, Nilaparvata lugens
by Biyun Wang, Zeping Mao, Youyuan Chen, Jinjun Ying, Haiqiang Wang, Zongtao Sun, Junmin Li, Chuanxi Zhang and Jichong Zhuo
Insects 2024, 15(4), 262; https://doi.org/10.3390/insects15040262 - 11 Apr 2024
Cited by 3 | Viewed by 2000
Abstract
The fruitless (fru) gene functions as a crucial “tuner” in male insect courtship behavior through distinct expression patterns. In Nilaparvata lugens, our previous research showed doublesex (dsx) influencing male courtship songs, causing mating failures with virgin females. However, [...] Read more.
The fruitless (fru) gene functions as a crucial “tuner” in male insect courtship behavior through distinct expression patterns. In Nilaparvata lugens, our previous research showed doublesex (dsx) influencing male courtship songs, causing mating failures with virgin females. However, the impact of fru on N. lugens mating remains unexplored. In this study, the fru homolog (Nlfru) in N. lugens yielded four spliceosomes: Nlfru-374-a/b, Nlfru-377, and Nlfru-433, encoding proteins of 374aa, 377aa, and 433aa, respectively. Notably, only Nlfru-374b exhibited male bias, while the others were non-sex-specific. All NlFRU proteins featured the BTB conserved domain, with NlFRU-374 and NlFRU-377 possessing the ZnF domain with different sequences. RNAi-mediated Nlfru or its isoforms’ knockdown in nymph stages blocked wing-flapping behavior in mating males, while embryonic knockdown via maternal RNAi resulted in over 80% of males losing wing-flapping ability, and female receptivity was reduced. Nlfru expression was Nldsx-regulated, and yet courtship signals and mating success were unaffected. Remarkably, RNAi-mediated Nlfru knockdown up-regulated the expression of flightin in macropterous males, which regulated muscle stiffness and delayed force response, suggesting Nlfru’s involvement in muscle development regulation. Collectively, our results indicate that Nlfru functions in N. lugens exhibit a combination of conservation and species specificity, contributing insights into fru evolution, particularly in Hemiptera species. Full article
(This article belongs to the Section Insect Behavior and Pathology)
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12 pages, 1975 KiB  
Article
Selection Signal Analysis Reveals Hainan Yellow Cattle Are Being Selectively Bred for Heat Tolerance
by Liuhao Wang, Xuehao Yan, Hongfen Wu, Feifan Wang, Ziqi Zhong, Gang Zheng, Qian Xiao, Kebang Wu and Wei Na
Animals 2024, 14(5), 775; https://doi.org/10.3390/ani14050775 - 29 Feb 2024
Cited by 2 | Viewed by 2013
Abstract
Hainan yellow cattle are indigenous Zebu cattle from southern China known for their tolerance of heat and strong resistance to disease. Generations of adaptation to the tropical environment of southern China and decades of artificial breeding have left identifiable selection signals in their [...] Read more.
Hainan yellow cattle are indigenous Zebu cattle from southern China known for their tolerance of heat and strong resistance to disease. Generations of adaptation to the tropical environment of southern China and decades of artificial breeding have left identifiable selection signals in their genomic makeup. However, information on the selection signatures of Hainan yellow cattle is scarce. Herein, we compared the genomes of Hainan yellow cattle with those of Zebu, Qinchuan, Nanyang, and Yanbian cattle breeds by the composite likelihood ratio method (CLR), Tajima’s D method, and identifying runs of homozygosity (ROHs), each of which may provide evidence of the genes responsible for heat tolerance in Hainan yellow cattle. The results showed that 5210, 1972, and 1290 single nucleotide polymorphisms (SNPs) were screened by the CLR method, Tajima’s D method, and ROH method, respectively. A total of 453, 450, and 325 genes, respectively, were identified near these SNPs. These genes were significantly enriched in 65 Gene Ontology (GO) functional terms and 11 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways (corrected p < 0.05). Five genes—Adenosylhomocysteinase-like 2, DnaJ heat shock protein family (Hsp40) member C3, heat shock protein family A (Hsp70) member 1A, CD53 molecule, and zinc finger and BTB domain containing 12—were recognized as candidate genes associated with heat tolerance. After further functional verification of these genes, the research results may benefit the understanding of the genetic mechanism of the heat tolerance in Hainan yellow cattle, which lay the foundation for subsequent studies on heat stress in this breed. Full article
(This article belongs to the Collection Advances in Cattle Breeding, Genetics and Genomics)
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18 pages, 1573 KiB  
Review
Zinc Finger and BTB Domain-Containing 20: A Newly Emerging Player in Pathogenesis and Development of Human Cancers
by Jiangyuan Liu and Han Zhang
Biomolecules 2024, 14(2), 192; https://doi.org/10.3390/biom14020192 - 4 Feb 2024
Cited by 2 | Viewed by 3292
Abstract
Zinc finger and BTB domain-containing 20 (ZBTB20), which was initially identified in human dendritic cells, belongs to a family of transcription factors (TFs) with an N-terminal BTB domain and one or more C-terminal DNA-binding zinc finger domains. Under physiological conditions, ZBTB20 acts as [...] Read more.
Zinc finger and BTB domain-containing 20 (ZBTB20), which was initially identified in human dendritic cells, belongs to a family of transcription factors (TFs) with an N-terminal BTB domain and one or more C-terminal DNA-binding zinc finger domains. Under physiological conditions, ZBTB20 acts as a transcriptional repressor in cellular development and differentiation, metabolism, and innate immunity. Interestingly, multiple lines of evidence from mice and human systems have revealed the importance of ZBTB20 in the pathogenesis and development of cancers. ZBTB20 is not only a hotspot of genetic variation or fusion in many types of human cancers, but also a key TF or intermediator involving in the dysregulation of cancer cells. Given the diverse functions of ZBTB20 in both health and disease, we herein summarize the structure and physiological roles of ZBTB20, with an emphasis on the latest findings on tumorigenesis and cancer progression. Full article
(This article belongs to the Topic Novel Discoveries in Oncology)
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18 pages, 5712 KiB  
Article
A Comprehensive Analysis of the Structural Recognition between KCTD Proteins and Cullin 3
by Nicole Balasco, Luciana Esposito, Giovanni Smaldone, Marco Salvatore and Luigi Vitagliano
Int. J. Mol. Sci. 2024, 25(3), 1881; https://doi.org/10.3390/ijms25031881 - 4 Feb 2024
Cited by 4 | Viewed by 1889
Abstract
KCTD ((K)potassium Channel Tetramerization Domain-containing) proteins constitute an emerging class of proteins involved in fundamental physio-pathological processes. In these proteins, the BTB domain, which represents the defining element of the family, may have the dual role of promoting oligomerization and favoring functionally important [...] Read more.
KCTD ((K)potassium Channel Tetramerization Domain-containing) proteins constitute an emerging class of proteins involved in fundamental physio-pathological processes. In these proteins, the BTB domain, which represents the defining element of the family, may have the dual role of promoting oligomerization and favoring functionally important partnerships with different interactors. Here, by exploiting the potential of recently developed methodologies for protein structure prediction, we report a comprehensive analysis of the interactions of all KCTD proteins with their most common partner Cullin 3 (Cul3). The data here presented demonstrate the impressive ability of this approach to discriminate between KCTDs that interact with Cul3 and those that do not. Indeed, reliable and stable models of the complexes were only obtained for the 15 members of the family that are known to interact with Cul3. The generation of three-dimensional models for all KCTD–Cul3 complexes provides interesting clues on the determinants of the structural basis of this partnership as clear structural differences emerged between KCTDs that bind or do not bind Cul3. Finally, the availability of accurate three-dimensional models for KCTD–Cul3 interactions may be valuable for the ad hoc design and development of compounds targeting specific KCTDs that are involved in several common diseases. Full article
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17 pages, 5644 KiB  
Article
The N-Terminal Part of Drosophila CP190 Is a Platform for Interaction with Multiple Architectural Proteins
by Anton Golovnin, Larisa Melnikova, Valentin Babosha, Galina V. Pokholkova, Ivan Slovohotov, Anastasia Umnova, Oksana Maksimenko, Igor F. Zhimulev and Pavel Georgiev
Int. J. Mol. Sci. 2023, 24(21), 15917; https://doi.org/10.3390/ijms242115917 - 2 Nov 2023
Cited by 9 | Viewed by 1801
Abstract
CP190 is a co-factor in many Drosophila architectural proteins, being involved in the formation of active promoters and insulators. CP190 contains the N-terminal BTB/POZ (Broad-Complex, Tramtrack and Bric a brac/POxvirus and Zinc finger) domain and adjacent conserved regions involved in protein interactions. Here, [...] Read more.
CP190 is a co-factor in many Drosophila architectural proteins, being involved in the formation of active promoters and insulators. CP190 contains the N-terminal BTB/POZ (Broad-Complex, Tramtrack and Bric a brac/POxvirus and Zinc finger) domain and adjacent conserved regions involved in protein interactions. Here, we examined the functional roles of these domains of CP190 in vivo. The best-characterized architectural proteins with insulator functions, Pita, Su(Hw), and dCTCF, interacted predominantly with the BTB domain of CP190. Due to the difficulty of mutating the BTB domain, we obtained a transgenic line expressing a chimeric CP190 with the BTB domain of the human protein Kaiso. Another group of architectural proteins, M1BP, Opbp, and ZIPIC, interacted with one or both of the highly conserved regions in the N-terminal part of CP190. Transgenic lines of D. melanogaster expressing CP190 mutants with a deletion of each of these domains were obtained. The results showed that these mutant proteins only partially compensated for the functions of CP190, weakly binding to selective chromatin sites. Further analysis confirmed the essential role of these domains in recruitment to regulatory regions associated with architectural proteins. We also found that the N-terminal of CP190 was sufficient for recruiting Z4 and Chromator proteins and successfully achieving chromatin opening. Taken together, our results and the results of previous studies showed that the N-terminal region of CP190 is a platform for simultaneous interaction with various DNA-binding architectural proteins and transcription complexes. Full article
(This article belongs to the Special Issue Molecular Genetics of Drosophila Development)
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