The GATA site-dependent hemogen promoter is transcriptionally regulated by GATA1 in hematopoietic and leukemia cells.
Hemgn (a gene symbol for hemogen in mouse, EDAG in human and RP59 in rat) encodes a nuclear protein that is highly expressed in hematopoietic tissues and acute leukemia. To characterize its regulatory mechanisms, we examined the activities of a Hemgn promoter containing 2975 bp of 5' flanking sequence and 196 bp of 5' untranslated region (5' UTR) sequence both in vitro and in vivo: this promoter is preferentially activated in a hematopoietic cell line, not in nonhematopoietic cell lines, and is sufficient to drive the transcription of a lacZ transgene in hematopoietic tissues in transgenic mice. Mutagenesis analyses showed that the 5' UTR including two highly conserved GATA boxes is critical for the promoter activity. GATA1, not GATA2, binds to the GATA binding sites and transactivates the Hemgn promoter in a dose-dependent manner. Furthermore, the expression of human hemogen (EDAG) transcripts were closely correlated with levels of GATA1 transcripts in primary acute myeloid leukemia specimens. This study suggests that the Hemgn promoter contains critical regulatory elements for its transcription in hematopoietic tissues and Hemgn is a direct target of GATA1 in leukemia cells.
Yang
L V
LV
Center for Molecular Medicine and Genetics, Wayne State University School of Medicine, Detroit, MI, USA.
Wan
J
J
Ge
Y
Y
Fu
Z
Z
Kim
S Y
SY
Fujiwara
Y
Y
Taub
J W
JW
Matherly
L H
LH
Eliason
J
J
Li
L
L
D020121:5' Untranslated Regions; D000818:Animals; D001483:Base Sequence; D001854:Bone Marrow Cells / Q000378:metabolism*; D045744:Cell Line, Tumor; D002648:Child; D004247:DNA; D050982:GATA1 Transcription Factor / Q000502:physiology*; D015973:Gene Expression Regulation, Leukemic; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics* / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000235:genetics*; D011401:Promoter Regions, Genetic; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic
D020121:5' Untranslated Regions; D050982:GATA1 Transcription Factor; C494688:GATA1 protein, human; C435745:HEMGN protein, human; D009687:Nuclear Proteins; D004247:DNA