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RNF220, an E3 ubiquitin ligase, is widely involved in neural development via targeting of multiple substrates. Here, we found that the expression of\n                    <jats:italic>Hox<\/jats:italic>\n                    genes in the pons was markedly up-regulated at the late developmental stage (post-embryonic day E15.5) in\n                    <jats:italic>\n                      Rnf220\n                      <jats:sup>-\/-<\/jats:sup>\n                    <\/jats:italic>\n                    and\n                    <jats:italic>\n                      Rnf220\n                      <jats:sup>+\/-<\/jats:sup>\n                    <\/jats:italic>\n                    mouse embryos. Single-nucleus RNA sequencing (RNA-seq) analysis revealed different\n                    <jats:italic>Hox<\/jats:italic>\n                    de-repression profiles in different groups of neurons, including the pontine nuclei (PN). The\n                    <jats:italic>Hox<\/jats:italic>\n                    pattern was disrupted and the neural circuits were affected in the PN of\n                    <jats:italic>\n                      Rnf220\n                      <jats:sup>+\/-<\/jats:sup>\n                    <\/jats:italic>\n                    mice. We showed that this phenomenon was mediated by WDR5, a key component of the TrxG complex, which can be polyubiquitinated and degraded by RNF220. Intrauterine injection of WDR5 inhibitor (WDR5-IN-4) and genetic ablation of\n                    <jats:italic>Wdr5<\/jats:italic>\n                    in\n                    <jats:italic>\n                      Rnf220\n                      <jats:sup>+\/-<\/jats:sup>\n                    <\/jats:italic>\n                    mice largely recovered the de-repressed\n                    <jats:italic>Hox<\/jats:italic>\n                    expression pattern in the hindbrain. In P19 embryonal carcinoma cells, the retinoic acid-induced\n                    <jats:italic>Hox<\/jats:italic>\n                    expression was further stimulated by\n                    <jats:italic>Rnf220<\/jats:italic>\n                    knockdown, which can also be rescued by\n                    <jats:italic>Wdr5<\/jats:italic>\n                    knockdown. In short, our data suggest a new role of RNF220\/WDR5 in\n                    <jats:italic>Hox<\/jats:italic>\n                    pattern maintenance and pons development in mice.\n                  <\/jats:p>","DOI":"10.7554\/elife.94657","type":"journal-article","created":{"date-parts":[[2024,4,3]],"date-time":"2024-04-03T11:26:24Z","timestamp":1712143584000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.94657","source":"Crossref","is-referenced-by-count":1,"title":["The E3 ubiquitin ligase RNF220 maintains hindbrain Hox expression patterns through regulation of WDR5 stability"],"prefix":"10.7554","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5755-6606","authenticated-orcid":true,"given":"Huishan","family":"Wang","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03m0vk445","id-type":"ROR","asserted-by":"publisher"}],"name":"Key Laboratory of Genetic Evolution and Animal Models, Kunming Institute of Zoology, Chinese Academy of 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