GATA2 and PU.1 collaborate to activate the expression of the mouse Ms4a2 gene, encoding Fc∈RIβ, through distinct mechanisms

Shin'ya Ohmori, Yasushi Ishijima, Suzuka Numata, Mai Takahashi, Masataka Sekita, Taichi Sato, Keisuke Chugun, Masayuki Yamamoto, Kinuko Ohneda

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

Abstract

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 (Fc∈RI). 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 Fc∈RI. 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.

Original languageEnglish
Article numbere00314-19
JournalMolecular and cellular biology
Volume39
Issue number22
DOIs
Publication statusPublished - 2019 Nov

Keywords

  • GATA transcription factors
  • High-affinity IgE receptor
  • Mast cell
  • Transcriptional regulation

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'GATA2 and PU.1 collaborate to activate the expression of the mouse Ms4a2 gene, encoding Fc∈RIβ, through distinct mechanisms'. Together they form a unique fingerprint.

Cite this