Khare SP, Shetty A, Biradar R, Patta I, Chen ZJ, Sathe AV, Reddy PC, Lahesmaa R and Galande S (2019) NF-κB Signaling and IL-4 Signaling Regulate SATB1 Expression via Alternative Promoter Usage During Th2 Differentiation. Front. Immunol. 10:667. doi: 10.3389/fimmu.2019.00667
NF-κB signaling and IL-4 signaling regulate SATB1 expression via alternative promoter usage during Th2 differentiation
|Author:||Khare, Satyajeet P.1,2; Shetty, Ankitha1,3; Biradar, Rahul1;|
1Center of Excellence in Epigenetics, Indian Institute of Science Education and Research, Pune, India
2Symbiosis School of Biological Sciences, Pune, India
3Turku Center for Biotechnology, University of Turku and Abo Akademi University, Turku, Finland
4Faculty of Biochemistry and Molecular Medicine, University of Oulu, Oulu,Finland
|Online Access:||PDF Full Text (PDF, 2.4 MB)|
|Persistent link:|| http://urn.fi/urn:nbn:fi-fe2021102252054
|Publish Date:|| 2021-10-26
SATB1 is a genome organizer protein that is expressed in a lineage specific manner in CD4+ T-cells. SATB1 plays a crucial role in expression of multiple genes throughout the thymic development and peripheral differentiation of T cells. Although SATB1 function has been subjected to intense investigation, regulation of SATB1 gene expression remains poorly understood. Analysis of RNA-seq data revealed multiple transcription start sites at the upstream regulatory region of SATB1. We further demonstrated that SATB1 gene is expressed via alternative promoters during T-helper (Th) cell differentiation. The proximal promoter “P1” is used more by the naïve and activated CD4+ T-cells whereas the middle “P2” and the distal “P3” promoters are used at a significantly higher level by polarized T-helper cells. Cytokine and TCR signaling play crucial roles toward SATB1 alternative promoter usage. Under Th2 polarization conditions, transcription factor STAT6, which operates downstream of the cytokine signaling binds to the P2 and P3 promoters. Genetic perturbation by knockout and chemical inhibition of STAT6 activation resulted in the loss of P2 and P3 promoter activity. Moreover, chemical inhibition of activation of NF-κB, a transcription factor that operates downstream of the TCR signaling, also resulted in reduced P2 and P3 promoter usage. Furthermore, usage of the P1 promoter correlated with lower SATB1 protein expression whereas P2 and P3 promoter usage correlated with higher SATB1 protein expression. Thus, the promoter switch might play a crucial role in fine-tuning of SATB1 protein expression in a cell type specific manner.
Frontiers in immunology
|Type of Publication:||
A1 Journal article – refereed
|Field of Science:||
Work in SG lab is supported by the Center of Excellence in Epigenetics program of the Department of Biotechnology, grant numbers BT/01/COE/09/07, BT/MED/30/SP11288/2015, and intramural funds from IISER Pune. RL has been supported by the Academy of Finland, AoF, Center of Excellence in Molecular Systems Immunology and Physiology Research (2012-2017) grant 250114; by the AoF grants 292335, 294337, 292482, 298732, 298998, 315585, and the Sigrid Jusélius Foundation (SJF). SK, AVS, and PR were supported by Post-Doctoral fellowships from IISER-Pune, DST-SERB (N-PDF), and DBT (RA), respectively. ZC was supported by the Academy of Finland, AoF grant 258313.
© 2019 Khare, Shetty, Biradar, Patta, Chen, Sathe, Reddy, Lahesmaa and Galande. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.