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

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.

SMAR1 repression by pluripotency factors and consequent chemoresistance in breast cancer stem-like cells is reversed by aspirin

“…To specifically target CSCs, the intricate signaling networks that are essential for driving the CSC function and phenotype thus need to be unraveled. SMAR1, previously known to function in chromatin remodeling, tissue-specific gene regulation, and tissue-specific metabolism (46), has been shown to induce tumor regression (47), and a diminished expression of SMAR1 is frequently associated with poor prognosis of various cancers (9). This protein not only serves as a attenuator of tumor proliferation and metastasis but also is an inducer of p53-mediated apoptosis (9).…”

Into the Fourth Dimension: Dysregulation of Genome Architecture in Aging and Alzheimer’s Disease

“…SATB1 has been shown previously to be important for anchoring chromatin loops on the beta-globin locus to bring the gene encoding the activated beta-globin subunit close to hypersensitive sites (i.e., enhancers), but segregate other genes away from this region (Wen et al, 2005 ; Wang et al, 2009 ). Indeed, S/MAR formation may help organize promoter-enhancer contacts, and dynamically regulate promoter activation (Figure 2 ; Padmaja et al, 2010 ; Mirlekar et al, 2017 ). SATB1-mediated chromatin looping is also involved in cytokine activation through the TH2-cytokine (IL4/5/13) locus in T-cells (Cai et al, 2006 ), regulation of the switch from the pro-apoptotic BCL2 gene to the anti-apoptotic NOXA gene (Yang et al, 2015 ), X-chromosome inactivation (Agrelo et al, 2009 ), as well as in regulating gene expression of the major histocompatibility complex (MHC) class I locus (Kumar et al, 2007 ).…”

“…This results in locus specific chromatin looping of local or distant genes that can be accessed by chromatin organizers. (A) SATB1-mediated looping at S/MARs can bring distal enhancers close to gene promoters and recruit histone acetyltransferase (HATs) for acetylation, resulting in RNA Pol II/TF recruitment and transcriptional activation (Wen et al, 2005 ; Wang et al, 2009 ; Padmaja et al, 2010 ; Mirlekar et al, 2017 ). (B) SATB1 can also segregate enhancers from promoters and recruit histone deacetylases (HDACs), resulting in facultative or constitutive repression (Padmaja et al, 2010 ; Kohwi-Shigematsu et al, 2013 ; Mirlekar et al, 2017 ).…”

Commitment to Aerobic Glycolysis Sustains Immunosuppression of Human Mesenchymal Stem Cells

“…The importance of metabolic control of cellular responses is increasingly appreciated in immune cells. Recent studies show that immune cell function is a product of their metabolic state and that different metabolic phenotypes instruct different effector functions including the appropriate immune polarization of cells in innate and adaptive immunity . For example, activated T‐cells undergo a metabolic reprogramming that promotes aerobic glycolysis for the elevated demands of biosynthesis, including the production of lipids, proteins, nucleic acids, and other carbohydrates .…”