Chromatin Remodeling Protein SMAR1 Is a Critical Regulator of T Helper Cell Differentiation and Inflammatory Diseases

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Mirlekar, Bhalchandra
- Affiliation: University of North Carolina at Chapel Hill
- Other Affiliation: Chromatin and Disease Biology Laboratory; National Centre for Cell Science
Gautam, Dipendra
- Affiliation: University of North Carolina at Chapel Hill
Chattopadhyay, Samit
- Other Affiliation: Cancer Biology and Inflammatory Disorder Division; Indian Institute of Chemical Biology

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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