ATF4 licenses C/EBPbeta activity in human mesenchymal stem cells primed for adipogenesis.
eLife. 2015;4:e06821.
- 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/EBPbeta 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/EBPbeta for genomic binding at a motif distinct from that bound by the C/EBPbeta homodimer. Our observations demonstrate that C/EBPbeta bridges the transcriptional programs in naive, confluent cells and early differentiating pre-adipocytes. Moreover, they suggest that homo- and heterodimer formation poise C/EBPbeta to execute diverse and stage-specific transcriptional programs by exploiting an expanded motif repertoire.
- Consortium data used in this publication
- ENCODE TF ChIP, DNase
- References