每年出版 6 期
ISSN 打印: 1040-8401
ISSN 在线: 2162-6472
Indexed in
Mechanisms of Transcriptional Regulation of the Human IL-3/GM-CSF Locus by Inducible Tissue-Specific Promoters and Enhancers
摘要
The IL-3 and GM-CSF genes are closely linked in the genome and reside within a cluster of cytokine genes. IL-3 and GM-CSF are expressed in a highly inducible and tissue-specific pattern, and this review attempts to provide a comprehensive description of the key regulatory elements in this locus that control their expression. Although these genes are typically coexpressed in T cells, they are differentially regulated in many other cell types, whereby cells such as monocytes and endothelial cells express GM-CSF, but not IL-3. This suggests that they are likely to be regulated by distinct mechanisms. This view is reinforced by the identification of three inducible enhancers in the locus that have different specificities. These enhancers are embedded within arrays of tissue-specific DNaseI hypersensitive sites that most likely play additional roles in establishing distinct patterns of gene expression. This locus also represents a valuable model system for studying the role of chromatin remodeling in cytokine gene activation. NFAT is one inducible factor that appears to play a major role in the formation of DNaseI hypersensitive sites within enhancers, and which functions in a highly cooperative manner with other classes of transcription factors to direct specific patterns of cytokine gene expression.
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Bowers Sarion R., Calero-Nieto Fernando J., Valeaux Stephanie, Fernandez-Fuentes Narcis, Cockerill Peter N., Runx1 binds as a dimeric complex to overlapping Runx1 sites within a palindromic element in the human GM-CSF enhancer, Nucleic Acids Research, 38, 18, 2010. Crossref
-
Oakford Phillippa C., James Sally R., Qadi Abeer, West Alison C., Ray Shannon N., Bert Andrew G., Cockerill Peter N., Holloway Adele F., Transcriptional and epigenetic regulation of the GM-CSF promoter by RUNX1, Leukemia Research, 34, 9, 2010. Crossref
-
Precht Patricia, Wurster Andrea L., Pazin Michael J., The SNF2H chromatin remodeling enzyme has opposing effects on cytokine gene expression, Molecular Immunology, 47, 11-12, 2010. Crossref
-
Wurster Andrea L., Precht Patricia, Pazin Michael J., NF-κB and BRG1 bind a distal regulatory element in the IL-3/GM-CSF locus, Molecular Immunology, 48, 15-16, 2011. Crossref
-
Pham Lan V., Tamayo Archito T., Li Changping, Bueso-Ramos Carlos, Ford Richard J., An epigenetic chromatin remodeling role for NFATc1 in transcriptional regulation of growth and survival genes in diffuse large B-cell lymphomas, Blood, 116, 19, 2010. Crossref
-
Cockerill Peter N., Structure and function of active chromatin and DNase I hypersensitive sites, FEBS Journal, 278, 13, 2011. Crossref
-
Borriello Francesco, Granata Francescopaolo, Marone Gianni, Basophils and Skin Disorders, Journal of Investigative Dermatology, 134, 5, 2014. Crossref
-
Livernois Alexandra, Hardy Kristine, Domaschenz Renae, Papanicolaou Alexie, Georges Arthur, Sarre Stephen D, Rao Sudha, Ezaz Tariq, Deakin Janine E, Identification of interleukin genes in Pogona vitticeps using a de novo transcriptome assembly from RNA-seq data, Immunogenetics, 68, 9, 2016. Crossref
-
Brignall Ruth, Cauchy Pierre, Bevington Sarah L., Gorman Bethany, Pisco Angela O., Bagnall James, Boddington Christopher, Rowe William, England Hazel, Rich Kevin, Schmidt Lorraine, Dyer Nigel P., Travis Mark A., Ott Sascha, Jackson Dean A., Cockerill Peter N., Paszek Pawel, Integration of Kinase and Calcium Signaling at the Level of Chromatin Underlies Inducible Gene Activation in T Cells, The Journal of Immunology, 199, 8, 2017. Crossref
-
KITAGISHI YASUKO, KOBAYASHI MAYUMI, YAMASHINA YURIE, MATSUDA SATORU, Elucidating the regulation of T cell subsets, International Journal of Molecular Medicine, 30, 6, 2012. Crossref
-
Pham Lan V., Bryant Jerry L., Yang David, Ford Richard J., Theranostic Approaches for Pathway-Activated Systems in Oncology, in Personalized Pathway-Activated Systems Imaging in Oncology, 2017. Crossref
-
Chen Guobao, Bracamonte-Baran William, Diny Nicola L., Hou Xuezhou, Talor Monica V., Fu Kai, Liu Yue, Davogustto Giovanni, Vasquez Hernan, Taegtmeyer Heinrich, Frazier O. Howard, Waisman Ari, Conway Simon J., Wan Fengyi, Čiháková Daniela, Sca-1+cardiac fibroblasts promote development of heart failure, European Journal of Immunology, 48, 9, 2018. Crossref
-
Peer Sebastian, Cappellano Giuseppe, Hermann-Kleiter Natascha, Albrecht-Schgoer Karin, Hinterleitner Reinhard, Baier Gottfried, Gruber Thomas, Regulation of Lymphatic GM-CSF Expression by the E3 Ubiquitin Ligase Cbl-b, Frontiers in Immunology, 9, 2018. Crossref
-
Baxter Euan W., Mirabella Fabio, Bowers Sarion R., James Sally R., Bonavita Aude-Marine, Bertrand Elisabeth, Strogantsev Ruslan, Hawwari Abbas, Bert Andrew G., Gonzalez de Arce Andrea, West Adam G., Bonifer Constanze, Cockerill Peter N., The Inducible Tissue-Specific Expression of the Human IL-3/GM-CSF Locus Is Controlled by a Complex Array of Developmentally Regulated Enhancers, The Journal of Immunology, 189, 9, 2012. Crossref
-
Bevington Sarah L, Cauchy Pierre, Piper Jason, Bertrand Elisabeth, Lalli Naveen, Jarvis Rebecca C, Gilding Liam Niall, Ott Sascha, Bonifer Constanze, Cockerill Peter N, Inducible chromatin priming is associated with the establishment of immunological memory in T cells, The EMBO Journal, 35, 5, 2016. Crossref
-
Mirabella Fabio, Baxter Euan W., Boissinot Marjorie, James Sally R., Cockerill Peter N., The Human IL-3/Granulocyte-Macrophage Colony-Stimulating Factor Locus Is Epigenetically Silent in Immature Thymocytes and Is Progressively Activated during T Cell Development, The Journal of Immunology, 184, 6, 2010. Crossref
-
Calero-Nieto Fernando J, Bert Andrew G, Cockerill Peter N, Transcription-dependent silencing of inducible convergent transgenes in transgenic mice, Epigenetics & Chromatin, 3, 1, 2010. Crossref
-
Chen X, Wang X, Hossain S, O'Neill F A, Walsh D, van den Oord E, Fanous A, Kendler K S, Interleukin 3 and schizophrenia: the impact of sex and family history, Molecular Psychiatry, 12, 3, 2007. Crossref
-
Kunnath-Velayudhan Shajo, Goldberg Michael F., Saini Neeraj K., Ng Tony W., Arora Pooja, Johndrow Christopher T., Saavedra-Avila Noemi Alejandra, Johnson Alison J., Xu Jiayong, Kim John, Khajoueinejad Nazanin, Petro Christopher D., Herold Betsy C., Lauvau Gregoire, Chan John, Jacobs William R., Porcelli Steven A., Generation of IL-3–Secreting CD4+ T Cells by Microbial Challenge at Skin and Mucosal Barriers, ImmunoHorizons, 3, 5, 2019. Crossref