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Regulation of early adipose commitment by Zfp521.

Publication ,  Journal Article
Kang, S; Akerblad, P; Kiviranta, R; Gupta, RK; Kajimura, S; Griffin, MJ; Min, J; Baron, R; Rosen, ED
Published in: PLoS Biol
2012

While there has been significant progress in determining the transcriptional cascade involved in terminal adipocyte differentiation, less is known about early events leading to lineage commitment and cell fate choice. It has been recently discovered that zinc finger protein 423 (Zfp423) is an early actor in adipose determination. Here, we show that a close paralog of Zfp423, Zfp521, acts as a key regulator of adipose commitment and differentiation in vitro and in vivo. Zfp521 exerts its actions by binding to early B cell factor 1 (Ebf1), a transcription factor required for the generation of adipocyte progenitors, and inhibiting the expression of Zfp423. Overexpression of Zfp521 in cells greatly inhibits adipogenic potential, whereas RNAi-mediated knock-down or genetic ablation of Zfp521 enhances differentiation. In addition, Zfp521⁻/⁻ embryos exhibit increased mass of interscapular brown adipose tissue and subcutaneous white adipocytes, a cell autonomous effect. Finally, Ebf1 participates in a negative feedback loop to repress Zfp521 as differentiation proceeds. Because Zfp521 is known to promote bone development, our results suggest that it acts as a critical switch in the commitment decision between the adipogenic and osteogenic lineages.

Duke Scholars

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Published In

PLoS Biol

DOI

EISSN

1545-7885

Publication Date

2012

Volume

10

Issue

11

Start / End Page

e1001433

Location

United States

Related Subject Headings

  • Transcriptional Activation
  • Transcription Factors
  • Trans-Activators
  • Repressor Proteins
  • Protein Interaction Mapping
  • Protein Binding
  • Mice, Nude
  • Mice
  • Male
  • Immunoprecipitation
 

Citation

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Kang, S., Akerblad, P., Kiviranta, R., Gupta, R. K., Kajimura, S., Griffin, M. J., … Rosen, E. D. (2012). Regulation of early adipose commitment by Zfp521. PLoS Biol, 10(11), e1001433. https://doi.org/10.1371/journal.pbio.1001433
Kang, Sona, Peter Akerblad, Riku Kiviranta, Rana K. Gupta, Shingo Kajimura, Michael J. Griffin, Jie Min, Roland Baron, and Evan D. Rosen. “Regulation of early adipose commitment by Zfp521.PLoS Biol 10, no. 11 (2012): e1001433. https://doi.org/10.1371/journal.pbio.1001433.
Kang S, Akerblad P, Kiviranta R, Gupta RK, Kajimura S, Griffin MJ, et al. Regulation of early adipose commitment by Zfp521. PLoS Biol. 2012;10(11):e1001433.
Kang, Sona, et al. “Regulation of early adipose commitment by Zfp521.PLoS Biol, vol. 10, no. 11, 2012, p. e1001433. Pubmed, doi:10.1371/journal.pbio.1001433.
Kang S, Akerblad P, Kiviranta R, Gupta RK, Kajimura S, Griffin MJ, Min J, Baron R, Rosen ED. Regulation of early adipose commitment by Zfp521. PLoS Biol. 2012;10(11):e1001433.
Journal cover image

Published In

PLoS Biol

DOI

EISSN

1545-7885

Publication Date

2012

Volume

10

Issue

11

Start / End Page

e1001433

Location

United States

Related Subject Headings

  • Transcriptional Activation
  • Transcription Factors
  • Trans-Activators
  • Repressor Proteins
  • Protein Interaction Mapping
  • Protein Binding
  • Mice, Nude
  • Mice
  • Male
  • Immunoprecipitation