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

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

Research output: Contribution to journalArticlepeer-review

39 Scopus citations


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
Issue numberJUNE 2015
StatePublished - Jun 25 2015
Externally publishedYes

ASJC Scopus subject areas

  • General Biochemistry, Genetics and Molecular Biology
  • General Immunology and Microbiology
  • General Neuroscience


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