1.Structural basis of INTAC-regulated transcription.
Hai ZHENG ; Qianwei JIN ; Xinxin WANG ; Yilun QI ; Weida LIU ; Yulei REN ; Dan ZHAO ; Fei XAVIER CHEN ; Jingdong CHENG ; Xizi CHEN ; Yanhui XU
Protein & Cell 2023;14(9):698-702
2.De novo construction of mammalian synthetic inhibitory transcription factor and promoter pairs.
Zijie YANG ; Yijie PAN ; Yiming CAI ; Tong FU ; Ao FENG ; Yan LIU ; Yiheng WANG ; Xinxuan XIONG ; Liang CAI
Chinese Journal of Biotechnology 2018;34(12):1886-1894
Transcriptional regulation is crucial for regulated gene expression. Due to the complexity, it has been difficult to engineer eukaryotic transcription factor (TF) and promoter pairs. The few availabilities of eukaryotic TF and promotor pairs limit their practical use for clinical or industrial applications. Here, we report a de novo construction of synthetic inhibitory transcription factor and promoter pairs for mammalian transcriptional regulation. The design of synthetic TF was based on the fusion of DNA binding domain and Kruppel associated box transcription regulating domain (KRAB). The synthetic promoter was constructed by inserting the corresponding TF response element after SV40 promoter. We constructed and tested five synthetic inhibitory transcription factor and promoter pairs in cultured mammalian cells. The inhibition capability and orthogonality were verified by flow cytometry. In summary, we demonstrate the feasibility of constructing mammalian inhibitory TF and promoter pairs, which could be standardized for advanced gene-circuit design and various applications in the mammalian synthetic biology.
Animals
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Gene Expression Regulation
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Gene Regulatory Networks
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Mammals
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Promoter Regions, Genetic
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Transcription Factors
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Transcription, Genetic
5.From tumor hypoxia to cancer progression: the implications of hypoxia-inducible factor-1 expression in cancers.
Fariz NURWIDYA ; Fumiyuki TAKAHASHI ; Kunihiko MINAKATA ; Akiko MURAKAMI ; Kazuhisa TAKAHASHI
Anatomy & Cell Biology 2012;45(2):73-78
Hypoxia, defined as a decrease of tissue oxygen levels, represents a fundamental pathophysiological condition in the microenvironment of solid tumors. Tumor hypoxia is known to be associated with radio/chemo-resistance and metastasis that eventually lead to cancer progression contributing to poor prognosis in cancer patients. Among transcription factors that accumulated under hypoxic conditions, hypoxia-inducible factor-1 (HIF-1) is a master transcription factor that has received the most intense attention in this field of research due to its capacity to modulate several hundred genes. With a clearer understanding of the HIF-1 pathway, efforts are directed at manipulation of this complex genetic process in order to ultimately decrease cellular HIF-1 levels. Some novel agents have been shown to have HIF-1 inhibition activity through a variety of molecular mechanisms and have provided promising results in the preclinical setting.
Anoxia
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Genetic Processes
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Humans
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Neoplasm Metastasis
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Oxygen
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Prognosis
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Transcription Factors
6.From tumor hypoxia to cancer progression: the implications of hypoxia-inducible factor-1 expression in cancers.
Fariz NURWIDYA ; Fumiyuki TAKAHASHI ; Kunihiko MINAKATA ; Akiko MURAKAMI ; Kazuhisa TAKAHASHI
Anatomy & Cell Biology 2012;45(2):73-78
Hypoxia, defined as a decrease of tissue oxygen levels, represents a fundamental pathophysiological condition in the microenvironment of solid tumors. Tumor hypoxia is known to be associated with radio/chemo-resistance and metastasis that eventually lead to cancer progression contributing to poor prognosis in cancer patients. Among transcription factors that accumulated under hypoxic conditions, hypoxia-inducible factor-1 (HIF-1) is a master transcription factor that has received the most intense attention in this field of research due to its capacity to modulate several hundred genes. With a clearer understanding of the HIF-1 pathway, efforts are directed at manipulation of this complex genetic process in order to ultimately decrease cellular HIF-1 levels. Some novel agents have been shown to have HIF-1 inhibition activity through a variety of molecular mechanisms and have provided promising results in the preclinical setting.
Anoxia
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Genetic Processes
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Humans
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Neoplasm Metastasis
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Oxygen
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Prognosis
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Transcription Factors
7.Progress of study on the transcription factor SALL4.
Jiang LIN ; Run-Bi JI ; Jun QIAN
Journal of Experimental Hematology 2011;19(3):820-823
SAL-like 4 (SALL4) locating at chromosome 20q13.13-13.2 encodes a newly identified transcription factor containing 8 zinc finger motif. Recent studies have revealed the important role of SALL4 gene in the regulation of early embryonic development, organogenesis, and proliferation and pluripotency of embryonic stem cells. The heterozygous mutations of SALL4 in different loci, causing nonsense mutation or frameshift mutation, and resulting in genesis of premature terminal codon, are correlated with autosomal dominant hereditary diseases such as Okihiro syndrome, acro-renal-ocular syndrome and IVIC syndrome. The level of SALL4 expression is increased in germ cell tumors, hepatoid gastric carcinoma, acute myeloid leukemia, B-precursor cell leukemia/lymphoma and myelodysplastic syndrome. This review focuses on the structure and function of SALL4 gene as well as its relevance to related diseases.
Genetic Diseases, Inborn
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genetics
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Humans
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Mutation
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Transcription Factors
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genetics
10.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