Atf4 licenses C/EBPβ activity in human mesenchymal stem cells primed for adipogenesis

Daniel M. Cohen, Kyoung Jae Won, Nha H. Nguyen, Mitchell A. Lazar, Christopher S. Chen, David J. Steger

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

A well-established cascade of transcription factor (TF) activity orchestrates adipogenesis in response to chemical cues, yet how cell-intrinsic determinants of differentiation such as cell shape and/or seeding density inform this transcriptional program remain enigmatic. Here, we uncover a novel mechanism licensing transcription in human mesenchymal stem cells (hMSCs) adipogenically primed by confluence. Prior to adipogenesis, confluency promotes heterodimer recruitment of the bZip TFs C/EBPβ and ATF4 to a non-canonical C/EBP DNA sequence. ATF4 depletion decreases both cell-density-dependent transcription and adipocyte differentiation. Global profiling in hMSCs and a novel cell-free assay reveals that ATF4 requires C/EBPβ for genomic binding at a motif distinct from that bound by the C/EBPβ homodimer. Our observations demonstrate that C/EBPβ bridges the transcriptional programs in na¨ıve, confluent cells and early differentiating preadipocytes. Moreover, they suggest that homo- and heterodimer formation poise C/EBPβ to execute diverse and stage-specific transcriptional programs by exploiting an expanded motif repertoire.

Original languageEnglish (US)
Article numbere06821
Pages (from-to)1-20
Number of pages20
JournaleLife
Volume4
Issue numberJUNE 2015
DOIs
StatePublished - Jun 25 2015
Externally publishedYes

Fingerprint

Adipogenesis
Transcription
Licensure
Stem cells
Mesenchymal Stromal Cells
Human Activities
DNA sequences
Assays
Transcription Factors
Cell Shape
Adipocytes
Cues
Cell Count

ASJC Scopus subject areas

  • Neuroscience(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

Cite this

Cohen, D. M., Won, K. J., Nguyen, N. H., Lazar, M. A., Chen, C. S., & Steger, D. J. (2015). Atf4 licenses C/EBPβ activity in human mesenchymal stem cells primed for adipogenesis. eLife, 4(JUNE 2015), 1-20. [e06821]. https://doi.org/10.7554/eLife.06821.001

Atf4 licenses C/EBPβ activity in human mesenchymal stem cells primed for adipogenesis. / Cohen, Daniel M.; Won, Kyoung Jae; Nguyen, Nha H.; Lazar, Mitchell A.; Chen, Christopher S.; Steger, David J.

In: eLife, Vol. 4, No. JUNE 2015, e06821, 25.06.2015, p. 1-20.

Research output: Contribution to journalArticle

Cohen, DM, Won, KJ, Nguyen, NH, Lazar, MA, Chen, CS & Steger, DJ 2015, 'Atf4 licenses C/EBPβ activity in human mesenchymal stem cells primed for adipogenesis', eLife, vol. 4, no. JUNE 2015, e06821, pp. 1-20. https://doi.org/10.7554/eLife.06821.001
Cohen, Daniel M. ; Won, Kyoung Jae ; Nguyen, Nha H. ; Lazar, Mitchell A. ; Chen, Christopher S. ; Steger, David J. / Atf4 licenses C/EBPβ activity in human mesenchymal stem cells primed for adipogenesis. In: eLife. 2015 ; Vol. 4, No. JUNE 2015. pp. 1-20.
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