Krüppel-like factor-6 promotes preadipocyte differentiation through histone deacetylase 3-dependent repression of DLK1

Dan Li, Steven Yea, Side Li, Zhu Chen, Goutham Narla, Michaela Banck, Jorge Laborda, Song Tan, Jeffrey M. Friedman, Scott L. Friedman, Martin J. Walsh

Research output: Contribution to journalArticle

114 Scopus citations

Abstract

Preadipocyte differentiation occurs during distinct periods of human development and is a key determinant of body mass. Transcriptional events underlying adipogenesis continue to emerge, but the link between chromatin remodeling of specific target loci and preadipocyte differentiation remains elusive. We have identified Krüppel-like factor-6 (KLF6), a recently described tumor suppressor gene, as a repressor of the proto-oncogene Delta-like 1 (DIk1), a gene encoding a transmembrane protein that inhibits adipocyte differentiation. Forced expression of KLF6 strongly inhibits Dlk1 expression in preadipocytes and NIH 3T3 cells in vivo, whereas down-regulation of KLF6 in 3T3-L1 cells by small interfering RNA prevents adipogenesis. Repression of Dlk1 requires HDAC3 deacetylase activity, which is recruited to the endogenous Dlk1 promoter where it interacts with KLF6. Our studies identify the interaction between HDAC3 and KLF6 as a potential mechanism underlying human adipogenesis, and highlight the role of KLF6 as a multifunctional transcriptional regulator capable of mediating adipocyte differentiation through gene repression.

Original languageEnglish (US)
Pages (from-to)26941-26952
Number of pages12
JournalJournal of Biological Chemistry
Volume280
Issue number29
DOIs
StatePublished - Jul 22 2005

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Li, D., Yea, S., Li, S., Chen, Z., Narla, G., Banck, M., Laborda, J., Tan, S., Friedman, J. M., Friedman, S. L., & Walsh, M. J. (2005). Krüppel-like factor-6 promotes preadipocyte differentiation through histone deacetylase 3-dependent repression of DLK1. Journal of Biological Chemistry, 280(29), 26941-26952. https://doi.org/10.1074/jbc.M500463200