The C/EBPβ LIP isoform rescues loss of C/EBPβ function in the mouse

Sci Rep. 2018 May 30;8(1):8417. doi: 10.1038/s41598-018-26579-y.

Abstract

The transcription factor C/EBPβ regulates hematopoiesis, bone, liver, fat, and skin homeostasis, and female reproduction. C/EBPβ protein expression from its single transcript occurs by alternative in-frame translation initiation at consecutive start sites to generate three isoforms, two long (LAP*, LAP) and one truncated (LIP), with the same C-terminal bZip dimerization domain. The long C/EBPβ isoforms are considered gene activators, whereas the LIP isoform reportedly acts as a dominant-negative repressor. Here, we tested the putative repressor functions of the C/EBPβ LIP isoform in mice by comparing monoallelic WT or LIP knockin mice with Cebpb knockout mice, in combination with monoallelic Cebpa mice. The C/EBPβ LIP isoform was sufficient to function in coordination with C/EBPα in murine development, adipose tissue and sebocyte differentiation, and female fertility. Thus, the C/EBPβ LIP isoform likely has more physiological functions than its currently known role as a dominant-negative inhibitor, which are more complex than anticipated.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3-L1 Cells
  • Adipose Tissue / metabolism
  • Alleles
  • Animals
  • CCAAT-Enhancer-Binding Protein-beta / deficiency
  • CCAAT-Enhancer-Binding Protein-beta / genetics*
  • CCAAT-Enhancer-Binding Protein-beta / metabolism*
  • Female
  • Fertility / genetics
  • Gene Knockout Techniques
  • Homeostasis
  • Mice
  • Phenotype
  • Protein Isoforms / deficiency
  • Protein Isoforms / genetics
  • Protein Isoforms / metabolism
  • Skin / metabolism

Substances

  • CCAAT-Enhancer-Binding Protein-beta
  • Protein Isoforms