Targeted deletion of a high-affinity GATA-binding site in the GATA-1 promoter leads to selective loss of the eosinophil lineage in vivo.
Transcription factor GATA-1 reprograms immature myeloid cells to three different hematopoietic lineages-erythroid cells, megakaryocytes, and eosinophils. GATA-1 is essential for maturation of erythroid and megakaryocytic precursors, as revealed by gene targeting in mice. Here we demonstrate that deletion of a high-affinity GATA-binding site in the GATA-1 promoter, an element presumed to mediate positive autoregulation of GATA-1 expression, leads to selective loss of the eosinophil lineage. These findings suggest that GATA-1 is required for specification of this lineage during hematopoietic development. Mice lacking the ability to produce eosinophils should prove useful in ascertaining the role of eosinophils in a variety of inflammatory or allergic disorders.
Yu
Channing
C
Department of Pediatric Oncology, Dana Farber Cancer Institute and Children's Hospital, Harvard Medical School, 300 Longwood Avenue, Boston, MA 02115, USA.
Cantor
Alan B
AB
Yang
Haidi
H
Browne
Carol
C
Wells
Richard A
RA
Fujiwara
Yuko
Y
Orkin
Stuart H
SH
D000818:Animals; D001483:Base Sequence; D002454:Cell Differentiation; D019070:Cell Lineage; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism*; D004804:Eosinophils / Q000166:cytology* / Q000378:metabolism; D050981:Erythroid-Specific DNA-Binding Factors; D004920:Erythropoiesis / Q000235:genetics; D050982:GATA1 Transcription Factor; D005786:Gene Expression Regulation; D015848:Interleukin-5 / Q000235:genetics / Q000378:metabolism; D019891:Leukopoiesis / Q000235:genetics; D008297:Male; D008407:Mast Cells / Q000166:cytology / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D011401:Promoter Regions, Genetic / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020218:Response Elements / Q000235:genetics*; D017384:Sequence Deletion; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism*
D004268:DNA-Binding Proteins; D050981:Erythroid-Specific DNA-Binding Factors; D050982:GATA1 Transcription Factor; C494689:Gata1 protein, mouse; D015848:Interleukin-5; D012333:RNA, Messenger; D014157:Transcription Factors