title: A long noncoding RNA transcriptional regulatory circuit drives thermogenic adipocyte differentiation.
abstract: Brown and beige/brite fats generate heat via uncoupled respiration to defend against cold. The total mass and activity of thermogenic adipose tissues are also tightly linked to systemic energy and nutrient homeostasis. Despite originating from distinct progenitors, brown and beige adipocytes acquire remarkably similar molecular and metabolic characteristics during differentiation through the action of a network of transcription factors and cofactors. How this regulatory network interfaces with long noncoding RNAs (lncRNAs), an emerging class of developmental regulators, remains largely unexplored. Here, we globally profiled lncRNA gene expression during thermogenic adipocyte formation and identified Brown fat lncRNA 1 (Blnc1) as a nuclear lncRNA that promotes brown and beige adipocyte differentiation and function. Blnc1 forms a ribonucleoprotein complex with transcription factor EBF2 to stimulate the thermogenic gene program. Further, Blnc1 itself is a target of EBF2, thereby forming a feedforward regulatory loop to drive adipogenesis toward thermogenic phenotype.
authors.affiliation: Life Sciences Institute and Department of Cell & Developmental Biology, University of Michigan Medical Center, Ann Arbor, MI 48109, USA.
authors.forename: Xu-Yun
authors.initials: XY
authors.lastname: Zhao
authors.affiliation: Life Sciences Institute and Department of Cell & Developmental Biology, University of Michigan Medical Center, Ann Arbor, MI 48109, USA.
authors.forename: Siming
authors.initials: S
authors.lastname: Li
authors.affiliation: Life Sciences Institute and Department of Cell & Developmental Biology, University of Michigan Medical Center, Ann Arbor, MI 48109, USA.
authors.forename: Guo-Xiao
authors.initials: GX
authors.lastname: Wang
authors.affiliation: Life Sciences Institute and Department of Cell & Developmental Biology, University of Michigan Medical Center, Ann Arbor, MI 48109, USA.
authors.forename: Qi
authors.initials: Q
authors.lastname: Yu
authors.affiliation: Life Sciences Institute and Department of Cell & Developmental Biology, University of Michigan Medical Center, Ann Arbor, MI 48109, USA. Electronic address: jdlin@umich.edu.
authors.forename: Jiandie D
authors.initials: JD
authors.lastname: Lin
mesh_terms: D050156:Adipogenesis; D002001:Adipose Tissue, Brown / Q000378:metabolism*; D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism*; D002460:Cell Line; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D057809:HEK293 Cells; D006801:Humans; D008297:Male; D008810:Mice, Inbred C57BL; D062085:RNA, Long Noncoding / Q000235:genetics / Q000378:metabolism*; D012261:Ribonucleoproteins / Q000378:metabolism
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D062085:RNA, Long Noncoding; D012261:Ribonucleoproteins