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Genetic analysis of transcription factors in dopaminergic neuronal development in Parkinson’s disease

Chinese Medical Journal 2024年第4期137卷 450-456页

作者： Yuwen Zhao Lixia Qin Hongxu Pan Tingwei Song Yige Wang Xiaoxia Zhou Yaqin Xiang Jinchen Li Zhenhua Liu Qiying Sun Jifeng Guo Xinxiang Yan Beisha Tang Qian Xu Department of Neurology Xiangya HospitalCentral South UniversityChangshaHunan 410008China Department of Neurology The Second Xiangya HospitalCentral South UniversityChangshaHunan 410011China Bioinformatics Center National Clinical Research Center for Geriatric Disorders Xiangya HospitalCentral South UniversityChangshaHunan 410008China Department of Geriatrics Xiangya HospitalCentral South UniversityChangshaHunan 410008China Centre for Medical Genetics and Hunan Key Laboratory of Medical Genetics School of Life SciencesCentral South UniversityChangshaHunan 410008China Key Laboratory of Hunan Province in Neurodegenerative Disorders Central South UniversityChangshaHunan 410008China

Background:Genetic variants of dopaminergic transcription factor-encoding genes are suggested to be Parkinson’s disease(PD)risk factors;however,no comprehensive analyses of these genes in patients with PD have been undertaken.Therefore,we aimed to genetically analyze 16 dopaminergic transcription factor genes in Chinese patients with PD.Methods:Whole-exome sequencing(WES)was performed using a Chinese cohort comprising 1917 unrelated patients with familial or sporadic early-onset PD and 1652 controls.Additionally,whole-genome sequencing(WGS)was performed using another Chinese cohort comprising 1962 unrelated patients with sporadic late-onset PD and 1279 controls.Results:We detected 308 rare and 208 rare protein-altering variants in the WES and WGS cohorts,respectively.Gene-based association analyses of rare variants suggested that MSX1 is enriched in sporadic late-onset PD.However,the significance did not pass the Bonferroni correction.Meanwhile,72 and 1730 common variants were found in the WES and WGS cohorts,respectively.Unfortunately,single-variant logistic association analyses did not identify significant associations between common variants and PD.Conclusions:Variants of 16 typical dopaminergic transcription factors might not be major genetic risk factors for PD in Chinese patients.However,we highlight the complexity of PD and the need for extensive research elucidating its etiology.

关键词： Parkinson’s disease transcription factors Dopaminergic neurons Genetic Variants

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The protein-protein interaction landscape of transcription factors during gynoecium development in Arabidopsis

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Molecular Plant 2023年第1期16卷 260-278页

作者： Humberto Herrera-Ubaldo Sergio E.Campos Pablo López-Gómez Valentín Luna-García Víctor M.Zúñiga-Mayo Gerardo E.Armas-Caballero Karla L.González-Aguilera Alexander DeLuna Nayelli Marsch-Martínez Carlos Espinosa-Soto Stefan de Folter Unidad de Genómica Avanzada(UGA-LANGEBIO) Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional(CINVESTAV-IPN)IrapuatoGuanajuato 36824México Departamento de Biotecnología y Bioquímica Unidad IrapuatoCINVESTAV-IPNIrapuatoGuanajuato 36824México Instituto de Física Universidad de San Luis PotosíSan Luis PotosíSLP 78290México Present address:Department of Plant Sciences University of CambridgeCambridgeUK Present address:Department of Molecular and Cellular Biology University of California DavisDavisCAUSA Present address:CONACYT Instituto de FitosanidadColegio de PostgraduadosCampus MontecilloTexcocoMéxico

Flowers are composed of organs whose identity is defined by the combinatorial activity of transcription factors(TFs).The interactions between MADS-box TFs and protein complex formation have been schematized in the floral quartet model of flower development.The gynoecium is the flower’s female reproductive part,crucial for fruit and seed production and,hence,for reproductive success.After the establishment of carpel identity,many tissues arise to form a mature gynoecium.TFs have been described as regulators of gynoecium development,and some interactions and complexes have been identified.However,broad knowledge about the interactions among these TFs and their participation during development remains scarce.In this study,we used a systems biology approach to understand the formation of a complex reproductive unit—as the gynoecium—by mapping binary interactions between well-characterized TFs.We analyzed almost 4500 combinations and detected more than 250 protein-protein interactions(PPIs),resulting in a process-specific interaction map.Topological analyses suggest hidden functions and novel roles for many TFs.In addition,we observed a close relationship between TFs involved in auxin and cytokinin-signaling pathways and other TFs.Furthermore,we analyzed the network by combining PPI data,expression,and genetic data,which helped us to dissect it into several dynamic spatio-temporal subnetworks related to gynoecium development processes.Finally,we generated an extended PPI network that predicts new players in gynoecium development.Taken together,all these results serve as a valuable resource for the plant community.

关键词： interactome networks transcription factors gynoecium development

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transcription factors specificity protein and nuclear receptor 4A1 in pancreatic cancer

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World Journal of Gastroenterology 2021年第38期27卷 6387-6398页

作者： Stephen Safe Rupesh Shrestha Kumaravel Mohankumar Marcell Howard Erik Hedrick Maen Abdelrahim Department of Veterinary Physiology and Pharmacology Texas A&M UniversityCollege StationTX 77845United States Department of Biochemistry and Biophysics Texas A&M UniversityCollege StationTX 77845United States Cancer Institute Cleveland ClinicClevelandOH 44195United States Department of Medical Oncology Houston Methodist Hospital Cancer CenterHoustonTX 77030United States

Specificity protein(Sp)transcription factors(TFs)Sp1,Sp3 and Sp4,and the orphan nuclear receptor 4A1(NR4A1)are highly expressed in pancreatic tumors and Sp1 is a negative prognostic factor for pancreatic cancer patient survival.Results of knockdown and overexpression of Sp1,Sp3 and Sp4 in pancreatic and other cancer lines show that these TFs are individually pro-oncogenic factors and loss of one Sp TF is not compensated by other members.NR4A1 is also a prooncogenic factor and both NR4A1 and Sp TFs exhibit similar functions in pancreatic cancer cells and regulate cell growth,survival,migration and invasion.There is also evidence that Sp TFs and NR4A1 regulate some of the same genes including survivin,epidermal growth factor receptor,PAX3-FOXO1,α5-andα6-integrins,β1-,β3-andβ4-integrins;this is due to NR4A1 acting as a cofactor and mediating NR4A1/Sp1/4-regulated gene expression through GC-rich gene promoter sites.Several studies show that drugs targeting Sp downregulation or NR4A1 antagonists are highly effective inhibitors of Sp/NR4A1-regulated pathways and genes in pancreatic and other cancer cells,and the triterpenoid celastrol is a novel dual-acting agent that targets both Sp TFs and NR4A1.

关键词： Specificity protein Nuclear receptor 4A1 Pancreatic cancer transcription factors Ligand inhibitors Nuclear receptor 4A antagonists

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Mechanisms and biotechnological applications of transcription factors

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Synthetic and Systems Biotechnology 2023年第4期8卷 565-577页

作者： Hehe He Mingfei Yang Siyu Li Gaoyang Zhang Zhongyang Ding Liang Zhang Guiyang Shi Youran Li Key Laboratory of Industrial Biotechnology Ministry of EducationSchool of BiotechnologyJiangnan UniversityWuxiJiangsu Province 214122PR China National Engineering Research Center of Cereal Fermentation and Food Biomanufacturing Jiangnan University1800 Lihu AvenueWuxiJiangsu Province 214122PR China Jiangsu Provisional Research Center for Bioactive Product Processing Technology Jiangnan University1800 Lihu AvenueWuxiJiangsu Province 214122PR China

transcription factors play an indispensable role in maintaining cellular viability and finely regulating complex internal metabolic networks.These crucial bioactive functions rely on their ability to respond to effectors and concurrently interact with binding sites.Recent advancements have brought innovative insights into the understanding of transcription factors.In this review,we comprehensively summarize the mechanisms by which transcription factors carry out their functions,along with calculation and experimental-based methods employed in their identification.Additionally,we highlight recent achievements in the application of transcription factors in various biotechnological fields,including cell engineering,human health,and biomanufacturing.Finally,the current limitations of research and provide prospects for future investigations are discussed.This review will provide enlightening theoretical guidance for transcription factors engineering.

关键词： transcription factors Binding sites Database-based prediction Experimental identification Cell engineering Biomanufacturing

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Three transcription factors and the way immune cells affected by different plasma change in opposite ways in the development of the syndrome of pre-eclampsia

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Chinese Medical Journal 2014年第12期127卷 2252-2258页

作者： Liang Zhou Zhu Jing Wang Yunfei Wang You Zhang Yu Lin Jianhua Di Wen Department of Obstetrics and Gynecology Ren Ji HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai 200127China Shanghai Key Laboratory of Gynecologic Oncology Shanghai 200127China

Background How the transcriptional factors regulated the innate and adaptive immune system in pregnancy and preeclampsia are less understood.Nevertheless,what the plasma work in the development of this disease was not sure.The present study was design to evaluate what the transcriptional factors change in innate and adaptive immune system and what the plasma do in this filed.Methods Peripheral blood mononuclear cells （PBMC） from non-pregnant women （n=18）,women with clinically normal pregnancies （n=23） and women with pre-eclampsia （n=20） were separated from peripheral blood to isolate monocytes and T cells.The purity of monocytes and T cells were analysed by flow cytometry.Monocytes and T cells were stimulated in either lipopolysaccharides （LPS） or phorbol-myristate-acetate （PMA）,respectively.transcription Factor Arrays were used to screen the transcription factors of interest in comparing of different groups.PBMC were isolated from another 8 nonpregnant samples were co-incubated with different groups of plasma.Polymerase chain reaction （PCR） was performed using whole cell extractions of the samples.Results Nuclear factor of activated T-cells-1 （NFAT-1）,signal transducers and activators of transcription-1 （STAT-1） and activator protein-1 （AP-1） are up-regulated in monocytes in pregnancy and more so in pre-eclampsia.On the the contrary,NFAT-1,STAT-1 and AP-1 are down-regulated in T cells in pregnancy and more so in pre-eclampsia.A reduction was observed in interferon （IFN）-y,interleukin （IL）-12 and IL-4 expression in T cells incubated with pre-eclamptic plasma.An elevation was observed in tumor necrosis factor （TNF）-α,IL-1 and IL-12 expression in monocytes incubated with preeclamptic plasma.Conclusions Innate immunity is over activated and adaptive immunity is over suppressed in the development of preeclampsia.NFAT-1,STAT-1 and AP-1 might be the central transcription factors in the pathogenesis of pre-eclampsia.They induced some changes in plasma and ＂educate＂ the monocytes and T cells for relevant cytokine product

关键词： pre-eclampsia monocytes T cells transcription factors

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Identification of Target Genes and transcription factors Implicated in Translation-Dependent Retrograde Sig- naling in Arabidopsis

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Molecular Plant 2014年第7期7卷 1228-1247页

作者： Dario Leister Isidora Romani Lukas Mittermayr Francesca Paieri Elena Fenino Tatjana Kleine Plant Molecular Biology (Botany) Department Biology I Ludwig-Maximilians-University Munich Gro0haderner Str. 2 D-82152Martinsried Germany

Changes in organellar gene expression （OGE） trigger retrograde signaling. The molecular dissection of OGE-dependent retrograde signaling based on analyses of mutants with altered OGE is complicated by compensatory responses that mask the primary signaling defect and by secondary effects that influence other retrograde signaling pathways. Therefore, to identify the earliest effects of altered OGE on nuclear transcript accumulation, we have induced OGE defects in adult plants by ethanol-dependent repression of PRORS1, which encodes a prolyl-tRNA synthetase located in chloroplasts and mitochondria. After 32 h of PRORS1 repression, the translational capacity of chloroplasts was reduced, and this effect subsequently intensified, while basic photosynthetic parameters were still unchanged at 51 h. Analysis of changes in whole-genome transcriptomes during exposure to ethanol revealed that induced PRORS1 silencing affects the expression of 1020 genes in all. Some of these encode photosynthesis-related proteins, including several down-regulated light-harvesting chlorophyll a/b binding （LHC） proteins. Interestingly, genes for presumptive endoplasmic reticulum pro- teins are transiently up-regulated. Furthermore, several NAC-domain-containing proteins are among the transcription factors regulated. Candidate cis-acting elements which may coordinate the transcriptional co-regulation of genes sets include both G-box variants and sequence motifs with no similarity to known plant c/s-elements.

关键词： Arabidopsis chloroplast mitochondrion retrograde signaling target genes transcription factors cis-elements.

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Molecular mechanisms of the suppression of axon regeneration by KLF transcription factors

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Neural Regeneration Research 2014年第15期9卷 1418-1421页

作者： Akintomide Apara Jeffrey L.Goldberg University of Miami Miller School of Medicine MiamiFL USA Shiley Eye CenterUniversity of California San Diego La JollaCA USA

Molecular mechanisms of the Kruppel-like family of transcription factors （KLFs） have been studied more in proliferating cells than in post-mitotic cells such as neurons. We recently found that KLFs regulate intrinsic axon growth ability in central nervous system （CNS） neurons in- cluding retinal ganglion cells, and hippocampal and cortical neurons. With at least 15 of 17 KLF family members expressed in neurons and at least 5 structurally unique subfamilies, it is import- ant to determine how this complex family functions in neurons to regulate the intricate genetic programs of axon growth and regeneration. By characterizing the molecular mechanisms of the KLF family in the nervous system, including binding partners and gene targets, and comparing them to defined mechanisms defined outside the nervous system, we may better understand how KLFs regulate neurite growth and axon regeneration.

关键词： optic nerve regeneration axon growth retina retinal ganglion cells spinal cord transcription factors

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Appadtion of the NAC transcription factors Predates the Emergence of Land Plants

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Molecular Plant 2016年第9期9卷 1345-1348页

作者： Aude Maugarny-Cales Beatriz Gonqalves Stefan Jouannic Michael Melkonian Gane Ka-Shu Wonge Patrick Laufs Institut Jean-Pierre Bourgin INRA AgroParisTech CNRS Universite ParisSaclay RD10 78026 Versailles Cedex France Univ. Pads-Sud Universite Paris-Saclay 91405 Orsay France IRD UMR DIADE 911 Avenue Agropolis BP6450134394 Mbntpellier Cedex 5 France LMI RICE IRD USTH National Key Laboratory for Plant Cell Biotechnology Agronomical Genetics Institute Pham Van Dong Road Hanoi Vietnam Botany Department Cologne Biocenter University of Cologne 50674 Cologne Germany Beijing Genomics Institute-Shenzhen Shenzhen 518083 China Department of Biological Sciences University of Alberta Edmonton AB T6G 2E9 Canada Department of Medicine University of Alberta Edmonton AB T6G 2E Canada These authors contributed equally to this article.

Dear Editor The NAC （for NO APICAL MERISTEM [NAM], Arabidopsis TRANSCRII^TION ACTIVATOR FACTOR [ATAF] and CUP- SHAPED COTYLEDON [CUC]） proteins are one of the largest families of plant-specific transcription factors （Nagata et aL, 2015）. They are involved in many different biological processes including development and the response to biotic and abiotic stresses. To date, NAC transcription factors have only been identified in land plants （Zhu et al., 2012; Nagata et al., 2015）; and some of them control land-plant-specific processes, such as the formation of specialized water-conducting systems （Xu et al., 2014）. Therefore, it has been suggested that their appearance accompanied the emergence of land plants. Here, we exploited the transcriptomic data generated within the 1000 plants project （***, Wickett et al., 2014） to revisit the origin of NAC proteins. Our careful analysis shows that NAC transcription factors appeared before the ernergence of land plants as we detected their homologs in several groups of streptophyte green algae. The possible significance of this finding is discussed.

关键词： transcription factors PLANT protein receptors PLANT genetics

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Culture conditions for equine bone marrow mesenchymal stem cells and expression of key transcription factors during their differentiation into osteoblasts

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Journal of Animal Science and Biotechnology 2014年第2期5卷 163-172页

作者： Elizabeth R A Glynn Alfredo Sanchez Londono Steven A Zinn Thomas A Hoagl Kristen E Govoni Department of Animal Science University of Connecticut3636 Horsebarn Road Ext.Unit 4040StorrsCT 06269-4040USA Department of Environmental and Population Health Tufts University North GraftonMA 01536USA

Background： The use of equine bone marrow mesenchymal stem cells （BMSC） is a novel method to improve fracture healing in horses. However, additional research is needed to identify optimal culture conditions and to determine the mechanisms involved in regulating BMSC differentiation into osteoblasts. The objectives of the experiments were to determine： 1） if autologous or commercial serum is better for proliferation and differentiation of equine BMSC into osteoblasts, and 2） the expression of key transcription factors during the differentiation of equine BMSC into osteoblasts. Equine BMSC were isolated from the sterna of 3 horses, treated with purchased fetal bovine serum （FBS） or autologous horse serum （HS）, and cell proliferation determined. To induce osteoblast differentiation, cells were incubated with L-ascorbic acid-2-phosphate and glycerol-2-phosphate in the presence or absence of human bone morphogenetic protein2 （BMP2）, dexamethasone （DEX）, or combination of the two. Alkaline phosphatase （ALP） activity, a marker of osteoblast differentiation, was determined by ELISA. Total RNA was isolated from differentiating BMSC between d 0 to 18 to determine expression of runt-reloted tronscrJption foctor2 （Runx2）, osterix （Osx）, and T-box3 （Tbx3）. Data were analyzed by ANOVA. Results： Relative to control, FBS and HS increased cell number （133 ± 5 and 116 ± 5%, respectively; P 〈 0.001） and 5-bromo- 2＇-deoxyuridine （BrdU） incorporation （167 ± 6 and 120 ± 6%, respectively; P 〈 0.001）. Treatment with DEX increased ALP activity compared with control （1,638 ± 38%; P 〈 0.001）. In the absence and presence of Dex, BMP-2 did not alter ALP activity （P 〉 0.8）. Runt-reloted transcription foctor2 expression increased 3-fold （P 〈 0.001） by d 6 of culture. Osterix expression increased 94old （P 〈 0.05） by d 18 of culture. Expression of Tbx3 increased 1.8-fold at d 3 （P 〈 0.01）; however expression was reduced 4-fold at d 18 （P 〈 0.01）. Conclusions： Dexamethasone, but not BMP-2, is required for differentiation of equine BMSC into osteo

关键词： Bone marrow mesenchymal stem cells Cell culture Equine Osteoblasts transcription factors

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Genome-wide Expansion and Expression Divergence of the Basic Leucine Zipper transcription factors in Higher Plants with an Emphasis on Sorghum

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Journal of Integrative Plant Biology 2011年第3期53卷 212-231页

作者： Jizhou Wang Junxia Zhou Baolan Zhang Jeevanandam Vanitha Srinivasan Ramachandran Shu-Ye Jiang Institute of Botany and Temasek Life Sciences Laboratory Joint Research & Development Laboratory Institute of Botany the Chinese Academy of Sciences Beijing 100093 China Temasek Life Sciences Laboratory 1 Research Link the National University of Singapore Singapore 117604 Singapore

Plant bZIP transcription factors play crucial roles in multiple biological processes. However, little is known about the sorghum bZIP gene family although the sorghum genome has been completely sequenced. In this study, we have carried out a genome-wide identification and characterization of this gene family in sorghum. Our data show that the genome encodes at least 92 bZIP transcription factors. These bZIP genes have been expanded mainly by segmental duplication. Such an expansion mechanism has also been observed in rice, arabidopsis and many other plant organisms, suggesting a common expansion mode of this gene family in plants. Further investigation shows that most of the bZIP members have been present in the most recent common ancestor of sorghum and rice and the major expansion would occur before the sorghum-rice split era. Although these bZlP genes have been duplicated with a long history, they exhibited limited functional divergence as shown by nonsynonymous substitutions （Ka）lsynonymous substitutions （Ks） analyses. Their retention was mainly due to the high percentages of expression divergence. Our data also showed that this gene family might play a role in multiple developmental stages and tissues and might be regarded as important regulators of various abiotic stresses and sugar signaling.

关键词： LEUCINE zippers transcription factors SORGHUM GENETICS PLANT genomes PLANT gene expression DIVERGENCE (Biology) CARRIER proteins

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