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Muscle regulatory factors are basic helix-loop-helix transcription factors that heterodimerize with E proteins to bind the regulatory regions of target genes. Their activity can be inhibited by members of the Inhibitor of DNA binding and differentiation (ID) family, which bind E-proteins with high affinity, thereby preventing muscle regulatory factor-dependent transcriptional responses. CCAAT\/Enhancer Binding protein beta (C\/EBP\u03b2) is a transcription factor expressed in myogenic precursor cells that acts to inhibit myogenic differentiation, though the mechanism remains poorly understood. We identify <jats:italic>Id3<\/jats:italic> as a novel C\/EBP\u03b2 target gene that inhibits myogenic differentiation. Overexpression of C\/EBP\u03b2 stimulates <jats:italic>Id3<\/jats:italic> mRNA and protein expression, and is required for C\/EBP\u03b2-mediated inhibition of myogenic differentiation. Misexpression of C\/EBP\u03b2 in myogenic precursors, such as in models of cancer cachexia, prevents the differentiation of myogenic precursors and we show that loss of <jats:italic>Id3<\/jats:italic> rescues differentiation under these conditions, suggesting that the stimulation of <jats:italic>Id3<\/jats:italic> expression by C\/EBP\u03b2 is an important mechanism by which C\/EBP\u03b2 inhibits myogenic differentiation.<\/jats:p>","DOI":"10.1038\/s41598-018-34871-0","type":"journal-article","created":{"date-parts":[[2018,11,5]],"date-time":"2018-11-05T14:23:29Z","timestamp":1541427809000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["CCAAT\/Enhancer Binding Protein \u03b2 inhibits myogenic differentiation via ID3"],"prefix":"10.1038","volume":"8","author":[{"given":"Hamood","family":"AlSudais","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Neena","family":"Lala-Tabbert","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8448-3246","authenticated-orcid":false,"given":"Nadine","family":"Wiper-Bergeron","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2018,11,9]]},"reference":[{"key":"34871_CR1","doi-asserted-by":"publisher","first-page":"215","DOI":"10.1002\/ar.1091820207","volume":"182","author":"R Bischoff","year":"1975","unstructured":"Bischoff, R. 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