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Transcriptional control of preadipocyte determination by Zfp423

Spiegelman, Bruce M ; Gupta, Rana K ; Arany, Zoltan ; Seale, Patrick ; Mepani, Rina J ; Ye, Li ; Conroe, Heather M ; Roby, Yang A ; Kulaga, Heather ; Reed, Randall R

Nature (London), 2010-03, Vol.464 (7288), p.619-623 [Periódico revisado por pares]

London: Nature Publishing Group

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Título:
Transcriptional control of preadipocyte determination by Zfp423
Autor: Spiegelman, Bruce M ; Gupta, Rana K ; Arany, Zoltan ; Seale, Patrick ; Mepani, Rina J ; Ye, Li ; Conroe, Heather M ; Roby, Yang A ; Kulaga, Heather ; Reed, Randall R
Assuntos: Adipose Tissue - cytology ; Animals ; Biological and medical sciences ; Care and treatment ; Cell Differentiation ; Cell differentiation, maturation, development, hematopoiesis ; Cell physiology ; DNA binding proteins ; DNA-Binding Proteins - metabolism ; Fat cells ; Female ; Fibroblasts ; Fundamental and applied biological sciences. Psychology ; Gene expression ; Gene Expression Regulation, Developmental ; Genetic aspects ; Methods ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Molecular and cellular biology ; NIH 3T3 Cells ; Obesity ; Physiological aspects ; PPAR gamma - metabolism ; Protein Structure, Tertiary ; Proteins ; Smad Proteins - metabolism ; Tissues ; Transcription Factors - metabolism
É parte de: Nature (London), 2010-03, Vol.464 (7288), p.619-623
Notas: ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
Current address: Cardiovascular Institute, Beth Israel Deaconess Medical Center, Harvard Medical School, Massachusetts 02115 USA
Descrição: The worldwide epidemic of obesity has increased the urgency to develop a deeper understanding of physiological systems related to energy balance and energy storage, including the mechanisms controlling the development of fat cells (adipocytes). The differentiation of committed preadipocytes to adipocytes is controlled by PPAR and several other transcription factors, but the molecular basis for preadipocyte determination is not understood. Using a new method for the quantitative analysis of transcriptional components, we identified the zinc-finger protein Zfp423 as a factor enriched in preadipose versus non-preadipose fibroblasts. Ectopic expression of Zfp423 in non-adipogenic NIH 3T3 fibroblasts robustly activates expression of Pparg in undifferentiated cells and permits cells to undergo adipocyte differentiation under permissive conditions. Short hairpin RNA (shRNA)-mediated reduction of Zfp423 expression in 3T3-L1 cells blunts preadipocyte Pparg expression and diminishes the ability of these cells to differentiate. Furthermore, both brown and white adipocyte differentiation is markedly impaired in Zfp423-deficient mouse embryos. Zfp423 regulates Pparg expression, in part, through amplification of the BMP signalling pathway, an effect dependent on the SMAD-binding capacity of Zfp423. This study identifies Zfp423 as a transcriptional regulator of preadipocyte determination.
Editor: London: Nature Publishing Group
Idioma: Inglês

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Transcriptional control of preadipocyte determination by Zfp423

Spiegelman, Bruce M ; Gupta, Rana K ; Arany, Zoltan ; Seale, Patrick ; Mepani, Rina J ; Ye, Li ; Conroe, Heather M ; Roby, Yang A ; Kulaga, Heather ; Reed, Randall R

London: Nature Publishing Group

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