TBX21

T-box transcription factor TBX21 is a protein that in humans is encoded by the TBX21 gene.^[1]

Function

This gene is a member of a phylogenetically conserved family of genes that share a common DNA-binding domain, the T-box. T-box genes encode transcription factors involved in the regulation of developmental processes. This gene is the human ortholog of mouse Tbx21/Tbet gene. Studies in mouse show that Tbx21 protein is a Th1 cell-specific transcription factor that controls the expression of the hallmark Th1 cytokine, interferon-gamma (IFNG). Expression of the human ortholog also correlates with IFNG expression in Th1 and natural killer cells, suggesting a role for this gene in initiating Th1 lineage development from naive Th precursor cells.^[1]

Role in disease

Asthma

The transcription factor encoded by TBX21 is T-bet, which regulates the development of naive T lymphocytes. Asthma is a disease of chronic inflammation, and it is known that transgenic mice born without TBX21 spontaneously develop abnormal lung function consistent with asthma. It is thought that TBX21, therefore, may play a role in the development of asthma in humans as well.^[2]

References

↑ ^1.0 ^1.1 “Entrez Gene: TBX21 T-box 21”.
↑ Tantisira KG, Hwang ES, Raby BA, Silverman ES, Lake SL, Richter BG, Peng SL, Drazen JM, Glimcher LH, and Weiss ST (Dec 2004). “TBX21: A functional variant predicts improvement in asthma with the use of inhaled corticosteroids”. PNAS. 101 (52): 18099–18104. doi:10.1073/pnas.0408532102. PMC 539815. PMID 15604153.

Maruyama K, Sugano S (Jan 1994). “Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides”. Gene. 138 (1–2): 171–4. doi:10.1016/0378-1119(94)90802-8. PMID 8125298.
Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S (Oct 1997). “Construction and characterization of a full length-enriched and a 5′-end-enriched cDNA library”. Gene. 200 (1–2): 149–56. doi:10.1016/S0378-1119(97)00411-3. PMID 9373149.
Szabo SJ, Kim ST, Costa GL, Zhang X, Fathman CG, Glimcher LH (Mar 2000). “A novel transcription factor, T-bet, directs Th1 lineage commitment”. Cell. 100 (6): 655–69. doi:10.1016/S0092-8674(00)80702-3. PMID 10761931.
Zhang WX, Yang SY (Nov 2000). “Cloning and characterization of a new member of the T-box gene family”. Genomics. 70 (1): 41–8. doi:10.1006/geno.2000.6361. PMID 11087660.
Faedo A, Ficara F, Ghiani M, Aiuti A, Rubenstein JL, Bulfone A (Aug 2002). “Developmental expression of the T-box transcription factor T-bet/Tbx21 during mouse embryogenesis”. Mechanisms of Development. 116 (1–2): 157–60. doi:10.1016/S0925-4773(02)00114-4. PMID 12128215.
Chung HT, Kim LH, Park BL, Lee JH, Park HS, Choi BW, Hong SJ, Chae SC, Kim JJ, Park CS, Shin HD (Sep 2003). “Association analysis of novel TBX21 variants with asthma phenotypes”. Human Mutation. 22 (3): 257. doi:10.1002/humu.9169. PMID 12938094.
Yu HR, Chang JC, Chen RF, Chuang H, Hong KC, Wang L, Yang KD (Nov 2003). “Different antigens trigger different Th1/Th2 reactions in neonatal mononuclear cells (MNCs) relating to T-bet/GATA-3 expression”. Journal of Leukocyte Biology. 74 (5): 952–8. doi:10.1189/jlb.0902474. PMID 12960249.
Lametschwandtner G, Biedermann T, Schwärzler C, Günther C, Kund J, Fassl S, Hinteregger S, Carballido-Perrig N, Szabo SJ, Glimcher LH, Carballido JM (May 2004). “Sustained T-bet expression confers polarized human TH2 cells with TH1-like cytokine production and migratory capacities”. The Journal of Allergy and Clinical Immunology. 113 (5): 987–94. doi:10.1016/j.jaci.2004.02.004. PMID 15131585.
Sasaki Y, Ihara K, Matsuura N, Kohno H, Nagafuchi S, Kuromaru R, Kusuhara K, Takeya R, Hoey T, Sumimoto H, Hara T (Aug 2004). “Identification of a novel type 1 diabetes susceptibility gene, T-bet”. Human Genetics. 115 (3): 177–84. doi:10.1007/s00439-004-1146-2. PMID 15241679.
Tantisira KG, Hwang ES, Raby BA, Silverman ES, Lake SL, Richter BG, Peng SL, Drazen JM, Glimcher LH, Weiss ST (Dec 2004). “TBX21: a functional variant predicts improvement in asthma with the use of inhaled corticosteroids”. Proceedings of the National Academy of Sciences of the United States of America. 101 (52): 18099–104. doi:10.1073/pnas.0408532102. PMC 539815. PMID 15604153.
Atayar C, Poppema S, Blokzijl T, Harms G, Boot M, van den Berg A (Jan 2005). “Expression of the T-cell transcription factors, GATA-3 and T-bet, in the neoplastic cells of Hodgkin lymphomas”. The American Journal of Pathology. 166 (1): 127–34. doi:10.1016/S0002-9440(10)62238-9. PMC 1602286. PMID 15632006.
Tong Y, Aune T, Boothby M (Feb 2005). “T-bet antagonizes mSin3a recruitment and transactivates a fully methylated IFN-gamma promoter via a conserved T-box half-site”. Proceedings of the National Academy of Sciences of the United States of America. 102 (6): 2034–9. doi:10.1073/pnas.0409510102. PMC 548570. PMID 15684083.
Dorfman DM, Hwang ES, Shahsafaei A, Glimcher LH (Jan 2005). “T-bet, a T cell-associated transcription factor, is expressed in Hodgkin’s lymphoma”. Human Pathology. 36 (1): 10–5. doi:10.1016/j.humpath.2004.10.006. PMID 15712176.
Kulkarni A, Ravi DS, Singh K, Rampalli S, Parekh V, Mitra D, Chattopadhyay S (Apr 2005). “HIV-1 Tat modulates T-bet expression and induces Th1 type of immune response”. Biochemical and Biophysical Research Communications. 329 (2): 706–12. doi:10.1016/j.bbrc.2005.02.042. PMID 15737643.
Akahoshi M, Obara K, Hirota T, Matsuda A, Hasegawa K, Takahashi N, Shimizu M, Nakashima K, Cheng L, Doi S, Fujiwara H, Miyatake A, Fujita K, Higashi N, Taniguchi M, Enomoto T, Mao XQ, Nakashima H, Adra CN, Nakamura Y, Tamari M, Shirakawa T (Jun 2005). “Functional promoter polymorphism in the TBX21 gene associated with aspirin-induced asthma”. Human Genetics. 117 (1): 16–26. doi:10.1007/s00439-005-1285-0. PMID 15806396.
Kawana K, Kawana Y, Schust DJ (Aug 2005). “Female steroid hormones use signal transducers and activators of transcription protein-mediated pathways to modulate the expression of T-bet in epithelial cells: a mechanism for local immune regulation in the human reproductive tract”. Molecular Endocrinology. 19 (8): 2047–59. doi:10.1210/me.2004-0489. PMID 15860546.
Harashima A, Matsuo Y, Drexler HG, Okochi A, Motoda R, Tanimoto M, Orita K (Jul 2005). “Transcription factor expression in B-cell precursor-leukemia cell lines: preferential expression of T-bet”. Leukemia Research. 29 (7): 841–8. doi:10.1016/j.leukres.2004.12.010. PMID 15927679.
Deng Y, Kerdiles Y, Chu J, Yuan S, Wang Y, Chen X, Mao H, Zhang L, Zhang J, Hughes T, Deng Y, Zhang Q, Wang F, Zou X, Liu CG, Freud AG, Li X, Caligiuri MA, Vivier E, Yu J (Mar 2015). “Transcription factor Foxo1 is a negative regulator of natural killer cell maturation and function”. Immunity. 42 (3): 457–70. doi:10.1016/j.immuni.2015.02.006. PMC 4400836. PMID 25769609.
Raby BA, Hwang ES, Van Steen K, Tantisira K, Peng S, Litonjua A, Lazarus R, Giallourakis C, Rioux JD, Sparrow D, Silverman EK, Glimcher LH, Weiss ST (Jan 2006). “T-bet polymorphisms are associated with asthma and airway hyperresponsiveness”. American Journal of Respiratory and Critical Care Medicine. 173 (1): 64–70. doi:10.1164/rccm.200503-505OC. PMC 2662983. PMID 16179640.

External links

TBX21+protein,+human at the US National Library of Medicine Medical Subject Headings (MeSH)

[entrez-1] 1.0 ^1.1 “Entrez Gene: TBX21 T-box 21”.

[Pubmed-2] Tantisira KG, Hwang ES, Raby BA, Silverman ES, Lake SL, Richter BG, Peng SL, Drazen JM, Glimcher LH, and Weiss ST (Dec 2004). “TBX21: A functional variant predicts improvement in asthma with the use of inhaled corticosteroids”. PNAS. 101 (52): 18099–18104. doi:10.1073/pnas.0408532102. PMC 539815. PMID 15604153.

[1]

[2]