GATA2 and PU.1 Collaborate To Activate the Expression of the Mouse Ms4a2 Gene, Encoding FcεRIβ, through Distinct Mechanisms

Mol Cell Biol. 2019 Oct 28;39(22):e00314-19. doi: 10.1128/MCB.00314-19. Print 2019 Nov 15.


GATA factors GATA1 and GATA2 and ETS factor PU.1 are known to function antagonistically during hematopoietic development. In mouse mast cells, however, these factors are coexpressed and activate the expression of the Ms4a2 gene encoding the β chain of the high-affinity IgE receptor (FcεRI). The present study showed that these factors cooperatively regulate Ms4a2 gene expression through distinct mechanisms. Although GATA2 and PU.1 contributed almost equally to Ms4a2 gene expression, gene ablation experiments revealed that simultaneous knockdown of both factors showed neither a synergistic nor an additive effect. A chromatin immunoprecipitation analysis showed that they shared DNA binding to the +10.4-kbp region downstream of the Ms4a2 gene with chromatin looping factor LDB1, whereas the proximal -60-bp region was exclusively bound by GATA2 in a mast cell-specific manner. Ablation of PU.1 significantly reduced the level of GATA2 binding to both the +10.4-kbp and -60-bp regions. Surprisingly, the deletion of the +10.4-kbp region by genome editing completely abolished the Ms4a2 gene expression as well as the cell surface expression of FcεRI. These results suggest that PU.1 and LDB1 play central roles in the formation of active chromatin structure whereas GATA2 directly activates the Ms4a2 promoter.

Keywords: GATA transcription factors; high-affinity IgE receptor; mast cell; transcriptional regulation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bone Marrow Cells / cytology
  • Chromatin Immunoprecipitation
  • DNA-Binding Proteins / metabolism
  • GATA2 Transcription Factor / genetics
  • GATA2 Transcription Factor / metabolism*
  • Gene Expression Regulation
  • LIM Domain Proteins / metabolism
  • Mast Cells / metabolism
  • Mice
  • Mice, Knockout
  • Promoter Regions, Genetic
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins / metabolism*
  • RNA, Messenger / genetics
  • RNA, Small Interfering / genetics
  • Receptors, IgE / genetics*
  • Receptors, IgE / metabolism
  • Trans-Activators / genetics
  • Trans-Activators / metabolism*


  • DNA-Binding Proteins
  • GATA2 Transcription Factor
  • Gata2 protein, mouse
  • LIM Domain Proteins
  • Ldb1 protein, mouse
  • Proto-Oncogene Proteins
  • RNA, Messenger
  • RNA, Small Interfering
  • Receptors, IgE
  • Trans-Activators
  • proto-oncogene protein Spi-1