Identification of regulatory elements that control PPAR? 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 PPAR? defines the adipose lineage, isolation of elements that control PPAR? 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 PPAR? locus that can drive expression of a reporter gene in a manner that recapitulates the tissue-specific pattern of PPAR? expression. Surprisingly, these 5 elements appear to control PPAR? expression in adipocyte precursors that are associated with the vasculature of adipose depots, but not in mature adipocytes. Characterization of these five PPAR? 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.

SUBMITTER: Chou WL 

PROVIDER: S-EPMC3757023 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature