{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Early B cell factor 1 (EBF1) is a pivotal “pioneer” transcription factor that plays a central role in establishing and maintaining B cell identity. EBF1 directly binds to key regulatory elements and collaborates with other lineage‐determining proteins—such as E2A and Pax5—to remodel chromatin, activate B lineage–specific gene expression (including genes encoding components of the B cell receptor) and simultaneously repress alternative cell fates (e.g., T cell or innate lymphoid programs)."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In addition, EBF1 is critical for establishing epigenetic programs during early B lymphopoiesis, as it not only activates clusters of B cell–expressed genes but also creates a chromatin environment that poises other genes for later activation; such roles are underscored by its regulation through distinct promoter elements and feedback circuits that fine‐tune its expression."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "4", "end_ref": "6"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Furthermore, in B cells undergoing somatic hypermutation—a process that risks mutagenesis across the genome—EBF1 (together with other key developmental regulators) is among a set of genes that are preferentially “protected” by high-fidelity DNA repair mechanisms, thereby maintaining genomic integrity during immune responses."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Notably, the functional repertoire of the EBF family extends beyond lymphopoiesis. For instance, in adipogenesis EBF1 actively contributes to the differentiation program by directly engaging and activating targets such as PPARγ, thereby influencing fat cell fate."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": " Moreover, genetic studies have positioned EBF1 downstream of regulators like Bcl11a—whose alterations are linked to leukemogenesis—further highlighting the decisive role of EBF1 in B cell development and its safeguarding functions in lineage fidelity."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Collectively, these studies demonstrate that EBF1 acts as a master regulator in B lymphocyte specification—by integrating upstream signals, directing chromatin remodeling, and orchestrating the transcriptional networks that promote B cell fate while inhibiting alternative lineage programs.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Yin C Lin, Suchit Jhunjhunwala, Christopher Benner, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A global network of transcription factors, involving E2A, EBF1 and Foxo1, that orchestrates B cell fate."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Immunol (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ni.1891"}], "href": "https://doi.org/10.1038/ni.1891"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20543837"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20543837"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Christopher S Seet, Rachel L Brumbaugh, Barbara L Kee "}, {"type": "b", "children": [{"type": "t", "text": "Early B cell factor promotes B lymphopoiesis with reduced interleukin 7 responsiveness in the absence of E2A."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Exp Med (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1084/jem.20032202"}], "href": "https://doi.org/10.1084/jem.20032202"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15210745"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15210745"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Robert Nechanitzky, Duygu Akbas, Stefanie Scherer, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Transcription factor EBF1 is essential for the maintenance of B cell identity and prevention of alternative fates in committed cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Immunol (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ni.2641"}], "href": "https://doi.org/10.1038/ni.2641"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23812095"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23812095"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Thomas Treiber, Elizabeth M Mandel, Sebastian Pott, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Early B cell factor 1 regulates B cell gene networks by activation, repression, and transcription- independent poising of chromatin."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Immunity (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.immuni.2010.04.013"}], "href": "https://doi.org/10.1016/j.immuni.2010.04.013"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20451411"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20451411"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Holly Maier, Rachel Ostraat, Hua Gao, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Early B cell factor cooperates with Runx1 and mediates epigenetic changes associated with mb-1 transcription."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Immunol (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ni1119"}], "href": "https://doi.org/10.1038/ni1119"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15361869"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15361869"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Stephanie Roessler, Ildiko Györy, Sascha Imhof, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Distinct promoters mediate the regulation of Ebf1 gene expression by interleukin-7 and Pax5."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell Biol (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1128/MCB.01192-06"}], "href": "https://doi.org/10.1128/MCB.01192-06"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17101802"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17101802"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Man Liu, Jamie L Duke, Daniel J Richter, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Two levels of protection for the B cell genome during somatic hypermutation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nature (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nature06547"}], "href": "https://doi.org/10.1038/nature06547"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18273020"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18273020"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Maria A Jimenez, Peter Akerblad, Mikael Sigvardsson, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Critical role for Ebf1 and Ebf2 in the adipogenic transcriptional cascade."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell Biol (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1128/MCB.01557-06"}], "href": "https://doi.org/10.1128/MCB.01557-06"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17060461"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17060461"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Pentao Liu, Jonathan R Keller, Mariaestela Ortiz, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Bcl11a is essential for normal lymphoid development."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Immunol (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ni925"}], "href": "https://doi.org/10.1038/ni925"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12717432"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12717432"}]}]}]}