title: Identification of regulatory elements that control PPARγ expression in adipocyte progenitors.
abstract: Adipose tissue renewal and obesity-driven expansion of fat cell number are dependent on proliferation and differentiation of adipose progenitors that reside in the vasculature that develops in coordination with adipose depots. The transcriptional events that regulate commitment of progenitors to the adipose lineage are poorly understood. Because expression of the nuclear receptor PPARγ defines the adipose lineage, isolation of elements that control PPARγ expression in adipose precursors may lead to discovery of transcriptional regulators of early adipocyte determination. Here, we describe the identification and validation in transgenic mice of 5 highly conserved non-coding sequences from the PPARγ locus that can drive expression of a reporter gene in a manner that recapitulates the tissue-specific pattern of PPARγ expression. Surprisingly, these 5 elements appear to control PPARγ expression in adipocyte precursors that are associated with the vasculature of adipose depots, but not in mature adipocytes. Characterization of these five PPARγ regulatory sequences may enable isolation of the transcription factors that bind these cis elements and provide insight into the molecular regulation of adipose tissue expansion in normal and pathological states.
authors.affiliation: Department of Chemical Physiology and The Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, California, USA.
authors.forename: Wen-Ling
authors.initials: WL
authors.lastname: Chou
authors.forename: Andrea
authors.initials: A
authors.lastname: Galmozzi
authors.forename: David
authors.initials: D
authors.lastname: Partida
authors.forename: Kevin
authors.initials: K
authors.lastname: Kwan
authors.forename: Hui
authors.initials: H
authors.lastname: Yeung
authors.forename: Andrew I
authors.initials: AI
authors.lastname: Su
authors.forename: Enrique
authors.initials: E
authors.lastname: Saez
mesh_terms: D017667:Adipocytes / Q000166:cytology / Q000378:metabolism*; D050156:Adipogenesis / Q000235:genetics; D002001:Adipose Tissue, Brown / Q000378:metabolism; D052436:Adipose Tissue, White / Q000378:metabolism; D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D017124:Conserved Sequence; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D056426:Genetic Loci; D051379:Mice; D008822:Mice, Transgenic; D009928:Organ Specificity / Q000235:genetics; D047495:PPAR gamma / Q000235:genetics* / Q000378:metabolism; D050436:Regulatory Elements, Transcriptional; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*; D015533:Transcriptional Activation
chemical_list: D047495:PPAR gamma