{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nVarious studies have demonstrated that coordinated transcriptional regulation by Egr family proteins and their NAB co‐regulators plays a critical role in controlling cellular differentiation and response to stress. In the heart, for instance, NAB1 is upregulated in heart failure and serves as an endogenous inhibitor of pathological cardiac hypertrophy by repressing Egr-dependent gene activation (for example, suppression of adrenergically induced and pressure overload‐induced hypertrophy), while in the peripheral nervous system, proper Schwann cell differentiation and myelination depend on the Egr2/NAB complex to promote cell cycle exit and activate myelin‑associated genes."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nMechanistic studies have further detailed that NAB corepressors not only assist Egr2 in activating myelin gene expression but also in directly repressing genes whose continued expression would hinder myelination. For instance, repressive complexes formed by Egrs (including Egr3) and NAB proteins recruit chromatin remodeling factors such as CHD4 to silence target genes during developmental transitions in both neural and myeloid cells, thereby modulating inflammatory responses through downregulation of receptors like IFNGR1."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn a more recent line of investigation, attention has turned to the RPEL1 gene, whose polymorphisms have been evaluated in Chinese systemic lupus erythematosus (SLE) patients. Unlike the extensively characterized NAB/Egr regulatory axis, RPEL1 remains less well defined functionally; however, its genetic variants (examined, for example, at rs4917385) may influence SLE susceptibility as well as modify clinical outcomes including glucocorticoid treatment efficacy, levels of anxiety and depression, and overall health‑related quality of life. These associations underscore a potential, albeit as yet poorly understood, role for RPEL1 in modulating immune and inflammatory pathways in autoimmunity and pave the way for further functional studies."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Monika Buitrago, Kristina Lorenz, Alexander H Maass, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The transcriptional repressor Nab1 is a specific regulator of pathological cardiac hypertrophy."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Med (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nm1272"}], "href": "https://doi.org/10.1038/nm1272"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16025126"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16025126"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Nam Le, Rakesh Nagarajan, James Y T Wang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Nab proteins are essential for peripheral nervous system myelination."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Neurosci (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nn1490"}], "href": "https://doi.org/10.1038/nn1490"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16136673"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16136673"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Gennifer M Mager, Rebecca M Ward, Rajini Srinivasan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Active gene repression by the Egr2.NAB complex during peripheral nerve myelination."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M803330200"}], "href": "https://doi.org/10.1074/jbc.M803330200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18456662"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18456662"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Staci J Kearney, Christine Delgado, Emily M Eshleman, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Type I IFNs downregulate myeloid cell IFN-γ receptor by inducing recruitment of an early growth response 3/NGFI-A binding protein 1 complex that silences ifngr1 transcription."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Immunol (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.4049/jimmunol.1203510"}], "href": "https://doi.org/10.4049/jimmunol.1203510"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23935197"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23935197"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Zi-Ye Yan, Wan-Qin Hu, Qi-Qun Zong, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Associations of RPEL1 and miR-1307 gene polymorphisms with disease susceptibility, glucocorticoid efficacy, anxiety, depression, and health-related quality of life in Chinese systemic lupus erythematosus patients."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Lupus (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1177/09612033221131182"}], "href": "https://doi.org/10.1177/09612033221131182"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "36194484"}], "href": "https://pubmed.ncbi.nlm.nih.gov/36194484"}]}]}]}