High-mobility group protein HMGB2 regulates human erythroid differentiation through trans-activation of GFI1B transcription

Blood. 2010 Jan 21;115(3):687-95. doi: 10.1182/blood-2009-06-230094. Epub 2009 Nov 24.

Abstract

Gfi-1B is a transcriptional repressor that is crucial for erythroid differentiation: inactivation of the GFI1B gene in mice leads to embryonic death due to failure to produce differentiated red cells. Accordingly, GFI1B expression is tightly regulated during erythropoiesis, but the mechanisms involved in such regulation remain partially understood. We here identify HMGB2, a high-mobility group HMG protein, as a key regulator of GFI1B transcription. HMGB2 binds to the GFI1B promoter in vivo and up-regulates its trans-activation most likely by enhancing the binding of Oct-1 and, to a lesser extent, of GATA-1 and NF-Y to the GFI1B promoter. HMGB2 expression increases during erythroid differentiation concomitantly to the increase of GfI1B transcription. Importantly, knockdown of HMGB2 in immature hematopoietic progenitor cells leads to decreased Gfi-1B expression and impairs their erythroid differentiation. We propose that HMGB2 potentiates GATA-1-dependent transcription of GFI1B by Oct-1 and thereby controls erythroid differentiation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • Cell Differentiation / drug effects
  • Cell Differentiation / genetics*
  • Cells, Cultured
  • Erythrocytes / drug effects
  • Erythrocytes / metabolism
  • Erythrocytes / physiology*
  • Erythroid Cells / drug effects
  • Erythroid Cells / metabolism
  • GATA1 Transcription Factor / metabolism
  • GATA1 Transcription Factor / physiology
  • HMGB2 Protein / antagonists & inhibitors
  • HMGB2 Protein / genetics
  • HMGB2 Protein / metabolism
  • HMGB2 Protein / physiology*
  • HeLa Cells
  • Humans
  • Molecular Sequence Data
  • Octamer Transcription Factor-1 / metabolism
  • Octamer Transcription Factor-1 / physiology
  • Promoter Regions, Genetic
  • Protein Binding
  • Proto-Oncogene Proteins / genetics*
  • Proto-Oncogene Proteins / metabolism
  • RNA, Small Interfering / pharmacology
  • Repressor Proteins / genetics*
  • Repressor Proteins / metabolism
  • Transcriptional Activation / drug effects

Substances

  • GATA1 Transcription Factor
  • GATA1 protein, human
  • GFI1B protein, human
  • HMGB2 Protein
  • Octamer Transcription Factor-1
  • Proto-Oncogene Proteins
  • RNA, Small Interfering
  • Repressor Proteins