Regulation of GATA factor expression is distinct between erythroid and mast cell lineages

Mol Cell Biol. 2012 Dec;32(23):4742-55. doi: 10.1128/MCB.00718-12. Epub 2012 Sep 17.

Abstract

The zinc finger transcription factors GATA1 and GATA2 participate in mast cell development. Although the expression of these factors is regulated in a cell lineage-specific and differentiation stage-specific manner, their regulation during mast cell development has not been clarified. Here, we show that the GATA2 mRNA level was significantly increased while GATA1 was maintained at low levels during the differentiation of mast cells derived from mouse bone marrow (BMMCs). Unlike in erythroid cells, forced expression or small interfering RNA (siRNA)-mediated knockdown of GATA1 rarely affected GATA2 expression, and vice versa, in mast cells, indicating the absence of cross-regulation between Gata1 and Gata2 genes. Chromatin immunoprecipitation assays revealed that both GATA factors bound to most of the conserved GATA sites of Gata1 and Gata2 loci in BMMCs. However, the GATA1 hematopoietic enhancer (G1HE) of the Gata1 gene, which is essential for GATA1 expression in erythroid and megakaryocytic lineages, was bound only weakly by both GATA factors in BMMCs. Furthermore, transgenic-mouse reporter assays revealed that the G1HE is not essential for reporter expression in BMMCs and peritoneal mast cells. Collectively, these results demonstrate that the expression of GATA factors in mast cells is regulated in a manner quite distinct from that in erythroid cells.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Bone Marrow Cells / cytology
  • Bone Marrow Cells / metabolism
  • Cell Differentiation*
  • Cell Lineage
  • Cells, Cultured
  • Erythroid Cells / cytology
  • Erythroid Cells / metabolism*
  • GATA1 Transcription Factor / genetics*
  • GATA1 Transcription Factor / metabolism
  • GATA2 Transcription Factor / genetics*
  • GATA2 Transcription Factor / metabolism
  • Gene Expression Regulation, Developmental*
  • Histones / genetics
  • Histones / metabolism
  • Male
  • Mast Cells / cytology
  • Mast Cells / metabolism*
  • Mice
  • Mice, Knockout
  • Protein Binding
  • RNA, Messenger / genetics

Substances

  • GATA1 Transcription Factor
  • GATA2 Transcription Factor
  • Gata1 protein, mouse
  • Gata2 protein, mouse
  • Histones
  • RNA, Messenger