1.Transcriptional activators and activation mechanisms.
Protein & Cell 2011;2(11):879-888
Transcriptional activators are required to turn on the expression of genes in a eukaryotic cell. Activators bound to the enhancer can facilitate either the recruitment of RNA polymerase II to the promoter or its elongation. This article examines a few selected issues in understanding activator functions and activation mechanisms.
Animals
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Humans
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Trans-Activators
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genetics
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metabolism
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Transcription Factors
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genetics
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metabolism
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Transcription, Genetic
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Transcriptional Activation
2.Overexpression of chicken Klf2 promotes klf7 transcription and inhibits adipocyte differentiation.
Qin GAO ; Hao ZHANG ; Yingjun WANG ; Xiaoling MU ; Zhiwei ZHANG
Chinese Journal of Biotechnology 2023;39(4):1670-1683
Overexpression of Krüppel like factor 2 (Klf2) or Klf7 inhibits adipocyte formation. However, it remains unclear whether Klf2 regulates klf7 expression in adipose tissue. In this study, oil red O staining and Western blotting were employed to study the effect of Klf2 overexpression on the differentiation of chicken preadipocytes. The results showed that Klf2 overexpression inhibited the differentiation of chicken preadipocytes induced by oleate and the expression of pparγ, while promoted klf7 expression in chicken preadipocytes. Spearman correlation analysis was used to study the correlation between the expression data of klf2 and klf7 in the adipose tissue of both human and chicken. The results showed that there was a significantly positive correlation between the expression of klf2 and klf7 in adipose tissues (r > 0.1). Luciferase reporter assay showed that overexpression of Klf2 significantly promoted the activity of chicken klf7 promoter (-241/-91, -521/-91, -1 845/-91, -2 286/-91, -1 215/-91; P < 0.05). In addition, the activity of klf7 promoter (-241/-91) reporter in chicken preadipocytes was significantly positively correlated with the amount of klf2 overexpression plasmid transfected (Tau=0.917 66, P=1.074×10-7). Moreover, Klf2 overexpression significantly promoted the mRNA expression of klf7 in chicken preadipocytes (P < 0.05). In conclusion, upregulation of klf7 expression might be one of the pathways that Klf2 inhibits chicken adipocyte differentiation, and the sequence from -241 bp to -91 bp upstream chicken klf7 translation start site might mediate the regulation of Klf2 on klf7 transcription.
Animals
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Humans
;
Chickens/genetics*
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Kruppel-Like Transcription Factors/metabolism*
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Transcription Factors/metabolism*
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Adipocytes/metabolism*
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Adipose Tissue/metabolism*
3.Heat shock transcription factor family in plants: a review.
Nan ZHANG ; Yinghong WANG ; Zhimin WANG ; Zhenyu YUE ; Yi NIU
Chinese Journal of Biotechnology 2021;37(4):1155-1167
With the constant change of global climate, plants are often affected by multiple abiotic stresses such as heat stress, drought stress, cold stress and saline-alkali stress. Heat shock transcription factors (HSFs) are a class of transcription factors widely existing in plants to respond to a variety of abiotic stresses. In this article, we review and summarize the structure, signal regulation mechanism of HSFs and some research in plants like Arabidopsis thaliana, tomato, rice and soybean, to provide reference for further elucidating the role of HSFs in the stress regulation network.
Arabidopsis/metabolism*
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Droughts
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Gene Expression Regulation, Plant
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Heat Shock Transcription Factors/genetics*
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Plant Proteins/genetics*
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Stress, Physiological
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Transcription Factors/metabolism*
4.Clinicopathological significance of increased ZIC1 expression in human endometrial cancer.
Xing GU ; Qin LIU ; Ning YANG ; Jian-fang SHEN ; Xue-gang ZHANG ; Fang CAO ; Hou-zhong DING
Journal of Huazhong University of Science and Technology (Medical Sciences) 2015;35(6):898-903
Zinc finger of the cerebellum (ZIC1), one of ZIC family genes, has been shown to play important roles in many cancers such as gastric cancer and breast cancer. However, there is little known about the expression and significance of ZIC1 in endometrial cancer. The aim of this study was to determine the expression pattern and clinicopathological significance of ZIC1 in endometrial cancer. The mRNA and protein expression of ZIC1 in endometrial cancer tissues was detected using the reverse-transcription polymerase chain reaction and Western blotting, respectively. Immunostaining of ZIC1 in 99 endometrial cancer samples was examined and its associations with clinicopathological parameters were analyzed. Hec-1-B cells were transfected with ZIC1-shRNA or sc-shRNA, and cell proliferation was assayed. Hec-1-B cells stably transfected with ZIC1-shRNA or sc-shRNA were subcutaneously inoculated into nude mice, and the tumor weight was measured. A significantly increased expression of ZIC1 mRNA and protein was observed in endometrial cancer tissues compared to that in normal endometrial tissues (P<0.05). Immunohistochemical analysis showed that strong cytoplasmic immunostaining of ZIC1 was observed in almost all endometrial cancer samples (90/99) while light and moderate immunostaining of ZIC1 was only detected in 17 of 30 (56.7%) normal tissues. Moreover, up-regulation of ZIC1 was significantly correlated with age, disease stage, TNM stage and FIGO stage (P<0.05). The down-regulated expression of ZIC1 contributed to the inhibition of cell proliferation, and inhibited the growth of tumor. It was concluded that ZIC1 is over-expressed in endometrial cancer tissue but not in normal tissue, and positively correlated to the malignant biological behavior of endometrial carcinogenesis.
Endometrial Neoplasms
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metabolism
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pathology
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Female
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Humans
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Middle Aged
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RNA, Messenger
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genetics
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Transcription Factors
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genetics
;
metabolism
5.Role of LNK gene mutation in pathogenesis of myeloproliferative neoplasms-review.
Yan CHEN ; Xue-Qiang WU ; Chun-Sheng HAN ; Ping ZHU ; Jun-Yan WEI
Journal of Experimental Hematology 2013;21(5):1309-1312
Myeloproliferative neoplasms ( MPN ) is a class of clonal hematopoietic stem cell disease. Studies found that the JAK-STAT signaling pathway is closely related to the pathogenesis of MPN. The lymphocyte-specific adaptor protein (LNK) gene negatively regulates Janus kinase-signal transducer and activator of transcription (JAK-STAT) signaling and may play an important role in the pathogenesis of MPN. Especially in JAK2 mutation-negative MPN, LNK gene specific mutations may be the key to cause MPN subtypes. Certain single nucleotide polymorphism of LNK gene regulation of hematopoietic cells in different directions may also be important influence factors of MPN performance for different subtypes. LNK gene functional changes lead to abnormal activation of the JAK-STAT signaling pathway, and may be a new mechanism of MPN. In this review, the role of LNK gene in MPN pathogenesis is briefly summarized.
Humans
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Janus Kinases
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metabolism
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Mutation
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Myeloproliferative Disorders
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genetics
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Proteins
;
genetics
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STAT Transcription Factors
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metabolism
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Signal Transduction
6.Regulation of plant MYB transcription factors in anther development.
Ruolin HU ; Chao YUAN ; Yi NIU ; Qinglin TANG ; Dayong WEI ; Zhimin WANG
Chinese Journal of Biotechnology 2020;36(11):2277-2286
MYB transcription factor is one of the largest transcription families and involved in plant growth and development, stress response, product metabolism and other processes. It regulates the development of plant flowers, especially anther development, a key role in the reproduction of plant progeny. Here, we discuss the regulatory effects of MYB transcription factors on the development of anther, including tapetum development, anther dehiscence, pollen development, carbohydrates and hormone pathways. We provide a reference for the further study of the regulation mechanism and network of plant anther development.
Arabidopsis/metabolism*
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Flowers/genetics*
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Gene Expression Regulation, Plant
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Humans
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Pollen/genetics*
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Reproduction
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Transcription Factors/metabolism*
7.Unveiling E2F4, TEAD1 and AP-1 as regulatory transcription factors of the replicative senescence program by multi-omics analysis.
Yuting WANG ; Liping LIU ; Yifan SONG ; Xiaojie YU ; Hongkui DENG
Protein & Cell 2022;13(10):742-759
Senescence, a stable state of growth arrest, affects many physiological and pathophysiological processes, especially aging. Previous work has indicated that transcription factors (TFs) play a role in regulating senescence. However, a systematic study of regulatory TFs during replicative senescence (RS) using multi-omics analysis is still lacking. Here, we generated time-resolved RNA-seq, reduced representation bisulfite sequencing (RRBS) and ATAC-seq datasets during RS of mouse skin fibroblasts, which demonstrated that an enhanced inflammatory response and reduced proliferative capacity were the main characteristics of RS in both the transcriptome and epigenome. Through integrative analysis and genetic manipulations, we found that transcription factors E2F4, TEAD1 and AP-1 are key regulators of RS. Overexpression of E2f4 improved cellular proliferative capacity, attenuated SA-β-Gal activity and changed RS-associated differentially methylated sites (DMSs). Moreover, knockdown of Tead1 attenuated SA-β-Gal activity and partially altered the RS-associated transcriptome. In addition, knockdown of Atf3, one member of AP-1 superfamily TFs, reduced Cdkn2a (p16) expression in pre-senescent fibroblasts. Taken together, the results of this study identified transcription factors regulating the senescence program through multi-omics analysis, providing potential therapeutic targets for anti-aging.
Aging
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Animals
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Cellular Senescence/genetics*
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E2F4 Transcription Factor/genetics*
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Fibroblasts/metabolism*
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Mice
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TEA Domain Transcription Factors/metabolism*
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Transcription Factor AP-1/metabolism*
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Transcriptome
8.Progress in the regulation of energy metabolic homeostasis by the SWI/SNF complex subunit Baf60a.
Mengyi XU ; Shiyao ZHANG ; Wenxiang ZHANG ; Chang LIU ; Siyu CHEN
Chinese Journal of Biotechnology 2021;37(2):500-512
Metabolic syndrome is a global chronic epidemic. Its pathogenesis is determined by genetic and environmental factors. Epigenetic modification is reported to regulate gene expression without altering its nucleotide sequences. In recent years, epigenetic modification is sensitively responded to environmental signals, further affecting the gene expression and signaling transduction. Among these regulators, chromatin remodeling SWI/SNF (SWItch/Sucrose non fermentable, SWI/SNF) complex subunit Baf60a plays an important role in maintaining energy homeostasis in mammals. In this paper, we described the pathophysiological roles of Baf60a in maintaining the balance of energy metabolism, including lipid metabolism, cholesterol metabolism, urea metabolism, as well as their rhythmicity. Therefore, in-depth understanding of Baf60a-orchestrated transcriptional network of energy metabolism will provide potential therapeutic targets and reliable theoretical supports for the treatment of metabolic syndrome.
Animals
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Energy Metabolism/genetics*
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Homeostasis
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Lipid Metabolism
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Signal Transduction
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Transcription Factors/metabolism*
9.ToxR represses the synthesis of c-di-GMP in Vibrio parahaemolyticus.
Miaomiao ZHANG ; Xingfan XUE ; Junfang SUN ; Qimin WU ; Xue LI ; Dongsheng ZHOU ; Bin NI ; Renfei LU ; Yiquan ZHANG
Chinese Journal of Biotechnology 2022;38(12):4719-4730
Vibrio parahaemolyticus, the main pathogen causing seafood related food poisoning worldwide, has strong biofilm formation ability. ToxR is a membrane binding regulatory protein, which has regulatory effect on biofilm formation of V. parahaemolyticus, but the specific mechanism has not been reported. c-di-GMP is an important second messenger in bacteria and is involved in regulating a variety of bacterial behaviors including biofilm formation. In this study, we investigated the regulation of ToxR on c-di-GMP metabolism in V. parahaemolyticus. Intracellular c-di-GMP in the wild type (WT) and toxR mutant (ΔtoxR) strains were extracted by ultrasonication, and the concentrations of c-di-GMP were then determined by enzyme linked immunosorbent assay (ELISA). Three c-di-GMP metabolism-related genes scrA, scrG and vpa0198 were selected as the target genes. Quantitative real-time PCR (q-PCR) was employed to calculate the transcriptional variation of each target gene between WT and ΔtoxR strains. The regulatory DNA region of each target gene was cloned into the pHR309 plasmid harboring a promoterless lacZ gene. The recombinant plasmid was subsequently transferred into WT and ΔtoxR strains to detect the β-galactosidase activity in the cellular extracts. The recombinant lacZ plasmid containing each of the target gene was also transferred into E. coli 100λpir strain harboring the pBAD33 plasmid or the recombinant pBAD33-toxR to test whether ToxR could regulate the expression of the target gene in a heterologous host. The regulatory DNA region of each target gene was amplified by PCR, and the over-expressed His-ToxR was purified. The electrophoretic mobility shift assay (EMSA) was applied to verify whether His-ToxR directly bound to the target promoter region. ELISA results showed that the intracellular c-di-GMP level significantly enhanced in ΔtoxR strain relative to that in WT strain, suggesting that ToxR inhibited the production of c-di-GMP in V. parahaemolyticus. qPCR results showed that the mRNA levels of scrA, scrG and vpa0198 significantly increased in ΔtoxR strain relative to those in WT strain, suggesting that ToxR repressed the transcription of scrA, scrG and vpa0198. lacZ fusion assay showed that ToxR was able to repress the promoter activities of scrA, scrG and vpa0198 in both V. parahaemolyticus and E. coli 100λpir. EMSA results showed that His-ToxR was able to bind to the regulatory DNA regions of scrA and scrG, but not to the regulatory DNA region of vpa0198. In conclusion, ToxR inhibited the production of c-di-GMP in V. parahaemolyticus via directly regulating the transcription of enzyme genes associated with c-di-GMP metabolism, which would be beneficial for V. parahaemolyticus to precisely control bacterial behaviors including biofilm formation.
Vibrio parahaemolyticus/metabolism*
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Escherichia coli/metabolism*
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Bacterial Proteins/metabolism*
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Transcription Factors/genetics*
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Gene Expression Regulation, Bacterial
10.The role of NAC transcription factors in flower development in plants.
Jiali WANG ; Hebing WANG ; Huiqin YANG ; Ruolin HU ; Dayong WEI ; Qinglin TANG ; Zhimin WANG
Chinese Journal of Biotechnology 2022;38(8):2687-2699
Transcription factors, the proteins with special structures, can bind to specific sites and regulate specific expression of target genes. NAC (NAM, ATAF1/2, CUC1/2) transcription factors, unique to plants, are composed of a conserved N-terminal domain and a highly variable C-terminal transcriptional activation domain. NAC transcription factors are involved in plant growth and development, responses to biotic and abiotic stresses and other processes, playing a regulatory role in flower development. In this paper, we reviewed the studies about NAC transcription factors in terms of discovery, structure, and regulatory roles in anther development, other floral organ development and flowering time. This review will provide a theoretical basis for deciphering the regulatory mechanism and improving the regulatory network of NAC transcription factors in flower development.
Flowers/genetics*
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Gene Expression Regulation, Plant
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Phylogeny
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Plant Proteins/metabolism*
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Plants/metabolism*
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Transcription Factors/metabolism*