Erythroid overexpression of C/EBPgamma in transgenic mice affects gamma-globin expression and fetal liver erythropoiesis

EMBO J. 2000 Nov 1;19(21):5856-63. doi: 10.1093/emboj/19.21.5856.

Abstract

The CCAAT boxes of the beta-like globin genes interact with three proteins: NF-Y, GATA-1 and NFE-6. We demonstrate that NFE-6 contains C/EBPgamma, and address its role in globin gene regulation by erythroid overexpression of C/EBPgamma, and a dominant-negative form C/EBPgammaDeltaB, in mice. Elevated levels of C/EBPgamma, but not C/EBPgammaDeltaB, increase expression of the (fetal) gamma-globin relative to the (adult) beta-globin gene. Interestingly, fetal liver erythropoiesis is ablated when the C/EBPgamma and C/EBPgammaDeltaB levels are further increased in homozygous transgenics. We suggest that targeted expression of dominant-negative leucine zipper proteins is a generally applicable approach to ablate specific tissues in mice.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • CCAAT-Binding Factor / genetics
  • CCAAT-Enhancer-Binding Proteins / genetics*
  • DNA Primers / genetics
  • DNA-Binding Proteins / genetics
  • Erythroid-Specific DNA-Binding Factors
  • Erythropoiesis / genetics*
  • Fetal Blood / cytology
  • Fetal Blood / metabolism
  • GATA1 Transcription Factor
  • Gene Expression Regulation, Developmental
  • Globins / genetics*
  • Leucine Zippers / genetics
  • Liver / embryology
  • Mice
  • Mice, Transgenic
  • Multigene Family
  • Transcription Factors / genetics

Substances

  • CCAAT-Binding Factor
  • CCAAT-Enhancer-Binding Proteins
  • CCAAT-enhancer-binding protein-gamma
  • DNA Primers
  • DNA-Binding Proteins
  • Erythroid-Specific DNA-Binding Factors
  • GATA1 Transcription Factor
  • Gata1 protein, mouse
  • Transcription Factors
  • Globins