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Chromatin Remodeling Protein SMAR1 Is a Critical Regulator of T Helper Cell Differentiation and Inflammatory Diseases
Bhalchandra Mirlekar1, Dipendra Gautam2, Samit Chattopadhyay3
1Chromatin and Disease Biology Laboratory, National Centre for Cell Science, Pune, India; Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC, USA.
Abstract:
T cell differentiation from naïve T cells to specialized effector subsets of mature cells is determined by the iterative action of transcription factors. At each stage of specific T cell lineage differentiation, transcription factor interacts not only with nuclear proteins such as histone and histone modifiers but also with other factors that are bound to the chromatin and play a critical role in gene expression. In this review, we focus on one of such nuclear protein known as tumor suppressor and scaffold matrix attachment region-binding protein 1 (SMAR1) in CD4+ T cell differentiation. SMAR1 facilitates Th1 differentiation by negatively regulating T-bet expression via recruiting HDAC1-SMRT complex to its gene promoter. In contrast, regulatory T (Treg) cell functions are dependent on inhibition of Th17-specific genes mainly IL-17 and STAT3 by SMAR1. Here, we discussed a critical role of chromatin remodeling protein SMAR1 in maintaining a fine-tuned balance between effector CD4+ T cells and Treg cells by influencing the transcription factors during allergic and autoimmune inflammatory diseases.
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