{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T15:34:31Z","timestamp":1781105671968,"version":"3.54.1"},"reference-count":47,"publisher":"National Academy of Sciences","issue":"19","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2006,5,9]]},"abstract":"<jats:p>\n                    Regulation of gene expression by tissue-specific transcription factors involves both turning on and turning off transcription of target genes. Runx3, a runt-domain transcription factor, regulates cell-intrinsic functions by activating and repressing gene expression in sensory neurons, dendritic cells (DC), and T cells. To investigate the mechanism of Runx3-mediated repression in an\n                    <jats:italic>in vivo<\/jats:italic>\n                    context, we generated mice expressing a mutant Runx3 lacking the C-terminal VWRPY, a motif required for Runx3 interaction with the corepressor Groucho\/transducin-like Enhancer-of-split (TLE). In contrast with Runx3\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice, which displayed ataxia due to the death of dorsal root ganglia TrkC neurons, Runx3\n                    <jats:sup>VWRPY\u2212\/\u2212<\/jats:sup>\n                    mice were not ataxic and had intact dorsal root ganglia neurons, indicating that ability of Runx3 to tether Groucho\/TLE is not essential for neurogenesis. In the DC compartment, the mutant protein Runx3\n                    <jats:sup>VWRPY\u2212<\/jats:sup>\n                    promoted normally developed skin Langerhans cells but failed to restrain DC spontaneous maturation, indicating that this latter process involves Runx3-mediated repression through recruitment of Groucho\/TLE. Moreover, in CD8\n                    <jats:sup>+<\/jats:sup>\n                    thymocytes, Runx3\n                    <jats:sup>VWRPY\u2212<\/jats:sup>\n                    up-regulated \u03b1\n                    <jats:italic>E<\/jats:italic>\n                    \/CD103-like WT Runx3, whereas unlike wild type, it failed to repress \u03b1\n                    <jats:italic>E<\/jats:italic>\n                    \/CD103 in CD8\n                    <jats:sup>+<\/jats:sup>\n                    splenocytes. Thus, in CD8-lineage T cells, Runx3 regulates \u03b1\n                    <jats:italic>E<\/jats:italic>\n                    \/CD103 in opposing regulatory modes and recruits Groucho\/TLE to facilitate the transition from activation to repression. Runx3\n                    <jats:sup>VWRPY\u2212<\/jats:sup>\n                    also failed to mediate the epigenetic silencing of\n                    <jats:italic>CD4<\/jats:italic>\n                    gene in CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells, but normally regulated other pan-CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cell genes. These data provide evidence for the requirement of Groucho\/TLE for Runx3-mediated epigenetic silencing of\n                    <jats:italic>CD4<\/jats:italic>\n                    and pertain to the mechanism through which other Runx3-regulated genes are epigenetically silenced.\n                  <\/jats:p>","DOI":"10.1073\/pnas.0602470103","type":"journal-article","created":{"date-parts":[[2006,5,1]],"date-time":"2006-05-01T20:21:18Z","timestamp":1146514878000},"page":"7384-7389","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":56,"title":["Groucho\/transducin-like Enhancer-of-split (TLE)-dependent and -independent transcriptional regulation by Runx3"],"prefix":"10.1073","volume":"103","author":[{"given":"Merav","family":"Yarmus","sequence":"first","affiliation":[{"name":"Department of Molecular Genetics, Weizmann Institute of Science, Rehovot 76100, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eilon","family":"Woolf","sequence":"additional","affiliation":[{"name":"Department of Molecular Genetics, Weizmann Institute of Science, Rehovot 76100, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yael","family":"Bernstein","sequence":"additional","affiliation":[{"name":"Department of Molecular Genetics, Weizmann Institute of Science, Rehovot 76100, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ofer","family":"Fainaru","sequence":"additional","affiliation":[{"name":"Department of Molecular Genetics, Weizmann Institute of Science, Rehovot 76100, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Varda","family":"Negreanu","sequence":"additional","affiliation":[{"name":"Department of Molecular Genetics, Weizmann Institute of Science, Rehovot 76100, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ditsa","family":"Levanon","sequence":"additional","affiliation":[{"name":"Department of Molecular Genetics, Weizmann Institute of Science, Rehovot 76100, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoram","family":"Groner","sequence":"additional","affiliation":[{"name":"Department of Molecular Genetics, Weizmann Institute of Science, Rehovot 76100, 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