title: A multifunctional protein, EWS, is essential for early brown fat lineage determination.
abstract: The recent surge in obesity has provided an impetus to better understand the mechanisms of adipogenesis, particularly in brown adipose tissue (BAT) because of its potential utilization for antiobesity therapy. Postnatal brown adipocytes arise from early muscle progenitors, but how brown fat lineage is determined is not completely understood. Here, we show that a multifunctional protein, Ewing Sarcoma (EWS), is essential for determining brown fat lineage during development. BATs from Ews null embryos and newborns are developmentally arrested. Ews mutant brown preadipocytes fail to differentiate due to loss of Bmp7 expression, a critical early brown adipogenic factor. We demonstrate that EWS, along with its binding partner Y-box binding protein 1 (YBX1), activates Bmp7 transcription. Depletion of either Ews or Ybx1 leads to loss of Bmp7 expression and brown adipogenesis. Remarkably, Ews null BATs and brown preadipocytes ectopically express myogenic genes. These results demonstrate that EWS is essential for early brown fat lineage determination.
authors.affiliation: Genetics of Development and Disease Branch, National Institute of Diabetes and Digestive and Kidney Diseases, 9000 Rockville Pike, Bethesda, MD 20892, USA.
authors.forename: Jun Hong
authors.initials: JH
authors.lastname: Park
authors.forename: Hong Jun
authors.initials: HJ
authors.lastname: Kang
authors.forename: Soo Im
authors.initials: SI
authors.lastname: Kang
authors.forename: Ji Eun
authors.initials: JE
authors.lastname: Lee
authors.forename: Jamie
authors.initials: J
authors.lastname: Hur
authors.forename: Kai
authors.initials: K
authors.lastname: Ge
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Mueller
authors.forename: Hongjie
authors.initials: H
authors.lastname: Li
authors.forename: Byeong-Chel
authors.initials: BC
authors.lastname: Lee
authors.forename: Sean Bong
authors.initials: SB
authors.lastname: Lee
mesh_terms: D052437:Adipocytes, Brown / Q000166:cytology / Q000378:metabolism; D050156:Adipogenesis / Q000235:genetics; D002001:Adipose Tissue, Brown / Q000166:cytology / Q000254:growth & development* / Q000378:metabolism*; D000818:Animals; D055419:Bone Morphogenetic Protein 7 / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics; D002460:Cell Line; D003080:Cold Temperature; D059305:Diet, High-Fat; D004622:Embryo, Mammalian / Q000166:cytology / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D005816:Genetic Complementation Test; D006801:Humans; D051379:Mice; D046912:Multiprotein Complexes / Q000378:metabolism; D024510:Muscle Development / Q000235:genetics; D034802:RNA-Binding Protein EWS / Q000235:genetics / Q000378:metabolism*; D022722:Thermogenesis / Q000235:genetics; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D055419:Bone Morphogenetic Protein 7; D046912:Multiprotein Complexes; D034802:RNA-Binding Protein EWS; D014157:Transcription Factors; C541744:Ybx1 protein, mouse