transcription factor

摘要： Proteomics is a powerful tool that can be used to elucidate the underlying mechanisms of diseases and identify new biomarkers.Therefore,it may also be helpful for understanding the detailed pathological mechanism of traumatic brain injury(TBI).In this study,we performed Tandem Mass Tag-based quantitative analysis of cortical proteome profiles in a mouse model of TBI.Our results showed that there were 302 differentially expressed proteins in TBI mice compared with normal mice 7 days after injury.Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses showed that these differentially expressed proteins were predominantly involved in inflammatory responses,including complement and coagulation cascades,as well as chemokine signaling pathways.Subsequent transcription factor analysis revealed that the inflammation-related transcription factors NF-κB1,RelA,IRF1,STAT1,and Spi1 play pivotal roles in the secondary injury that occurs after TBI,which further corroborates the functional enrichment for inflammatory factors.Our results suggest that inflammation-related proteins and inflammatory responses are promising targets for the treatment of TBI.

摘要： The transcription factor Sox11 plays important roles in retinal neurogenesis during vertebrate eye development.However,its function in retina regeneration remains elusive.Here we report that Sox11 b,a zebrafish Sox11 homolog,regulates the migration and fate determination of Müller glia-derived progenitors(MGPCs)in an adult zebrafish model of mechanical retinal injury.Following a stab injury,the expression of Sox11 b was induced in proliferating MGPCs in the retina.Sox11 b knockdown did not affect MGPC formation at 4 days post-injury,although the nuclear morphology and subsequent radial migration of MGPCs were alte red.At 7 days post-injury,Sox11 b knockdown res ulted in an increased proportion of MGPCs in the inner retina and a decreased propo rtion of MGPCs in the outer nuclear layer,compared with controls.Furthermore,Sox11 b knockdown led to reduced photoreceptor regeneration,while it increased the numbe rs of newborn amacrines and retinal ganglion cells.Finally,quantitative polymerase chain reaction analysis revealed that Sox11 b regulated the expression of Notch signaling components in the retina,and Notch inhibition partially recapitulated the Sox11 b knockdown phenotype,indicating that Notch signaling functions downstream of Sox11 b.Our findings imply that Sox11 b plays key roles in MGPC migration and fate determination during retina regeneration in zebrafish,which may have critical im plications for future explorations of retinal repair in mammals.

摘要： Chx10-expressing V2 a(Chx10+V2 a) spinal interneurons play a large role in the excitatory drive of motoneurons. Chemogenetic ablation studies have demonstrated the essential nature of Chx10+V2 a interneurons in the regulation of locomotor initiation, maintenance, alternation, speed, and rhythmicity. The role of Chx10+V2 a interneurons in locomotion and autonomic nervous system regulation is thought to be robust, but their precise role in spinal motor regulation and spinal cord injury have not been fully explored. The present paper reviews the origin, characteristics, and functional roles of Chx10+V2 a interneurons with an emphasis on their involvement in the pathogenesis of spinal cord injury. The diverse functional properties of these cells have only been substantiated by and are due in large part to their integration in a variety of diverse spinal circuits. Chx10+V2 a interneurons play an integral role in conferring locomotion, which integrates various corticospinal, mechanosensory, and interneuron pathways. Moreover, accumulating evidence suggests that Chx10+V2 a interneurons also play an important role in rhythmic patterning maintenance, leftright alternation of central pattern generation, and locomotor pattern generation in higher order mammals, likely conferring complex locomotion. Consequently, the latest research has focused on postinjury transplantation and noninvasive stimulation of Chx10+V2 a interneurons as a therapeutic strategy, particularly in spinal cord injury. Finally, we review the latest preclinical study advances in laboratory derivation and stimulation/transplantation of these cells as a strategy for the treatment of spinal cord injury. The evidence supports that the Chx10+V2 a interneurons act as a new therapeutic target for spinal cord injury. Future optimization strategies should focus on the viability, maturity, and functional integration of Chx10+V2 a interneurons transplanted in spinal cord injury foci.

摘要： After brain injury, infiltration and abnormal activation of neutrophils damages brain tissue and worsens inflammation, but the mediators that connect activated neutrophils with neuroinflammation have not yet been fully clarified. To identify regulators of neutrophil-mediated neuroinflammation after traumatic brain injury, a mouse model of traumatic brain injury was established by controlled cortical impact. At 7 days post-injury(sub-acute phase), genome-wide transcriptomic data showed that interleukin 17 A-associated signaling pathways were markedly upregulated, suggesting that interleukin 17 A may be involved in neuroinflammation. Double immunofluorescence staining showed that interleukin 17 A was largely secreted by neutrophils rather than by glial cells and neurons. Furthermore, nuclear factor-kappaB and Stat3, both of which are important effectors in interleukin 17 A-mediated proinflammatory responses, were significantly activated. Collectively, our findings suggest that neutrophil-derived interleukin 17 A participates in neutrophil-mediated neuroinflammation during the subacute phase of traumatic brain injury. Therefore, interleukin 17 A may be a promising therapeutic target for traumatic brain injury.

摘要： Egfr,a member of the ErbB gene family,plays a critical role in tissue development and homeostasis,wound healing,and disease.However,expression and regulators of Egfr during spinal cord development remain poorly understood.In this study,we investigated ErbB evolution and analyzed co-expression modules,miRNAs,and transcription factors that may regulate Egfr expression in rats.We found that ErbB family members formed via Egfr duplication in the ancient ve rtebrates but dive rged after speciation of gnathostomes.We identified a module that was co-expressed with Egfr,which involved cell proliferation and blood vessel development.We predicted 25 miRNAs and nine transcription factors that may regulate Egfr expression.Dual-luciferase reporter assays showed six out of nine transcription factors significantly affected Egfr promoter reporter activity.Two of these transcription factors(KLF1 and STAT3)inhibited the Egfr promoter repo rter,whereas four transcription factors(including FOXA2)activated the Egfr promoter reporter.Real-time PCR and immunofluorescence expe riments showed high expression of FOXA2 during the embryonic period and FOXA2 was expressed in the floor plate of the spinal cord,suggesting the importance of FOXA2 during embryonic spinal cord development.Considering the importance of Egfr in embryonic spinal cord development,wound healing,and disease(specifically in cancer),regulatory elements identified in this study may provide candidate targets for nerve regeneration and disease treatment in the future.

摘要： Lettuce(Lactuca sativa L.),which belongs to the large Asteraceae(Compositae)family,breeds by sexual reproduction and produces seeds.Actually,lettuce seeds are achenes,which are defined as fruits.However,few studies have described the morphological characteristics of the lettuce achenes,and genes essential for achene development are largely unknown in lettuce.To investigate the gene activity during achene development and determine the possible mechanisms that influence achene development in lettuce,we performed a time-course transcriptome analysis of lettuce achenes.A total of 27,390 expressed genes were detected at the five achene development stages.We investigated the gene expression patterns during achene development and identified the enriched biological processes at the corresponding stages.Kyoto Encyclopedia of Genes and Genomes and Gene Ontology analyses revealed a variety of transcriptomic similarities and differences at different achene development stages.Further,transcription factors and phytohormones were found to play important roles during achene development.Finally,we proposed a working model to illustrate the gene expression modules and possible molecular mechanisms underlying achene development.Our time-course transcriptome data also provide a foundation for future functional studies to reveal the genetic control of achene development in lettuce.

摘要： Nuclear factor kB(NF-kB)is a ubiquitous regulator of the signalome and is indispensable for various biological cell functions.NF-kB consists of five transcription factors that execute both cytoplasmic and nuclear signaling processes in cells.NF-kB is the only signaling molecule that governs both pro-and antiapoptotic,and pro-and anti-inflammatory responses.This is due to the canonical and non-canonical components of the NF-kB signaling pathway.Together,these pathways orchestrate cancer-related inflammation,hyperplasia,neoplasia,and metastasis.Non-canonical NF-kB pathways are particularly involved in the chemoresistance of cancer cells.In view of its pivotal role in cancer progression,NF-kB represents a potentially significant therapeutic target for modifying tumor cell behavior.Several phytochemicals are known to modulate NF-kB pathways through the stabilization of its inhibitor,IkB,by inhibiting phosphorylation and ubiquitination thereof.Several natural pharmacophores are known to inhibit the nuclear translocation of NF-kB and associated pro-inflammatory responses and cell survival pathways.In view of this and the high degree of specificity exhibited by various phytochemicals for the NF-kB component,we herein present an in-depth overview of these phytochemicals and discuss their mode of interaction with the NF-kB signaling pathways for controlling the fate of tumor cells for cancerdirected interventions.

摘要： The SRY-related high mobility group(HMG)box(SOX)transcription factors participate in many physiological processes of animal growth,development,and reproduction and are related to spermatogenesis in many species.However,the relationship between SOX and spermatogenesis in Eriocheir sinensis is rarely reported.Here,we studied the role of Es-SOX8 in the spermatogenesis of E.sinensis and its possible regulation mechanism.Immunofluorescence results demonstrated Es-SOX8 signal in both cytoplasm and nucleus of spermatogonia,spermatocytes as well as spermatids,but not in mature spermatozoa.Hematoxylin and eosin staining showed a significant increase in the number of spermatozoa with abnormal nuclear morphology in vivo,described as prominent edges and corners,after the knockdown of Es-SOX8 through RNA interference.This indicated a possible role of Es-SOX8 in the nuclear deformation process in the spermatogenesis of E.sinensis.Analysis of the mRNA levels of Es-bone morphogenetic protein 2(BMP2)in the Es-Sox8 knocked-down testis tissue revealed significantly decreased transcription of Es-BMP2.Chromatin immunoprecipitation results showed the binding of Es-SOX8 protein to the promoter region of Es-BMP2.Thus,Es-SOX8 can directly regulate the transcription of Es-BMP2 by activating the promoter of Es-BMP2 and thus affects the sperm nucleus deformation of E.sinensis.

摘要： The divergence and continuous evolution of plants and animals contribute to ecological diversity.Promoters and transcription factors(TFs) are key determinants of gene regulation and transcription throughoutlife.However,theevolutionary trajectories and relationships of promoters and TFs are still poorly understood. Here, we conducted extensive analysis of large-scale multi-omics sequences in 420 animal species and 223 plant species spanning nearly a billion years of evolutionary history. Results showed that promoter GC-contentandTFisoelectricpoints,as features/signatures that accompany long biological evolution, exhibited increasing growth in animal cells but a decreasing trend in plant cells. Furthermore, the evolutionary trajectories of promoter and TF signatures in the animal kingdom provided further evidence that Mammalia as well as Aves evolved directly from the ancestor Reptilia. The strong correlation between promoter and TF signatures indicates that promoters and TFs formed antagonistic coevolution in the animal kingdom, but mutualistic coevolution in the plant kingdom. The distinct coevolutionary patterns potentially drive the plant-animal divergence, divergent evolution and ecological diversity.

摘要： As a macronutrient,Phosphorus(P)takes many roles in plant growth and development.It should be significant to explore the molecular mechanism of low-phosphorus stress response of plants.Phosphate starvation response(PHR)transcription factors play important roles in response to phosphorus deficiency stress in plants.In this study,we isolated a gene related to the plant phosphorus signaling system from the acid-soil-resistant centipedegrass(Eremochloa ophiuroides[Munro]Hack.),termed EoPHR2.The subcellular localization of EoPHR2 protein was observed to be nuclear located.The expression patterns of EoPHR2 in different tissues and Al/Pi-stress conditions were analyzed by qRT-PCR,they suggested a potential role in response to the multiple-stress under acid soil adversity.Based on the functional identification through transgenic plants,we found that(1)EoPHR2 is involved in the Pi-signaling pathway,and(2)overexpression of EoPHR2 mimics Pi-starvation signalling resulting on enhanced roots whether under Pi-deficiency stress or not.In conclusion,EoPHR2 transcription factor plays a role in response to the multiple stresses under acid soil conditions,improving the low-phosphorus stress resistance of Eremochloa ophiuroides.