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PMID: 8474451 Published · ppublish English Comparative Study Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Mouse beta-globin DNA-binding protein B1 is identical to a proto-oncogene, the transcription factor Spi-1/PU.1, and is restricted in expression to hematopoietic cells and the testis.

Molecular and cellular biology ·Vol. 13 ·No. 5 ·1993-05-00 ·Pages 2929-41

Galson DL, Hensold JO, Bishop TR, Schalling M, D'Andrea AD, Jones C, Auron PE, Housman DE

Abstract

The hematopoietic-specific DNA-binding protein B1 binds to the DNA consensus sequence AAAGRGGAARYG located twice in intervening sequence 2 of both of the mouse beta-globin genes (D. L. Galson and D.E. Housman, Mol. Cell. Biol. 8:381-392, 1988). B1 was cloned by expression of a murine erythroleukemia (MEL) cell cDNA library in transfected COS cells and screening by electrophoretic mobility shift analysis. B1 is identical to the proto-oncogene Spi-1/PU.1 (Spi-1), an ets family member. Protein-DNA contacts are shown to resemble those of the helix-turn-helix homeodomain proteins. By Northern (RNA) analysis, we found that Spi-1 mRNA is present at low levels during murine CFU-E maturation and is at least 20-fold higher in uninduced MEL, a transformed proerythroblast-like cell line which contains an activating/transforming insertion of spleen focus-forming virus at the Spi-1 locus. Dimethyl sulfoxide-induced MEL cell differentiation decreases Spi-1 mRNA to approximately 20% of the uninduced level before commitment occurs. In addition to erythroid cells, Spi-1 mRNA is present in B cells, myelomonocytes, and mast cells but not in T cells and nonhematopoietic cell types. In situ hybridization demonstrated Spi-1 mRNA expression in bone marrow, spleen, interstitial nonhepatocytes of the liver, and interstitial nontubular cells of the testis. The Spi-1 locus was mapped on human chromosome 11 to the same interval as ACP2 (lysosomal acid phosphatase), between the anonymous DNA markers D11S33 and D11S14. This region has not yet been found to be associated with a human malignancy.

Related Genes
MeSH Terms
Amino Acid Sequence Animals Base Sequence Cell Line Chromosome Mapping Chromosomes, Human, Pair 11 DNA/genetics,metabolism DNA-Binding Proteins/genetics,metabolism Erythrocytes/physiology Gene Expression Globins/genetics Hematopoietic Stem Cells/physiology Humans In Situ Hybridization Leukemia, Erythroblastic, Acute/genetics Male Mice Mice, Inbred BALB C Molecular Sequence Data Multigene Family Oncogenes Organ Specificity Proto-Oncogene Mas Proto-Oncogenes RNA, Messenger/genetics,metabolism Retroviridae Proteins, Oncogenic/genetics Sequence Homology, Amino Acid Sequence Homology, Nucleic Acid Spleen/physiology Testis/physiology Transcription Factors/genetics,metabolism Transfection Tumor Cells, Cultured
Chemicals
DNA-Binding Proteins MAS1 protein, human Proto-Oncogene Mas RNA, Messenger Retroviridae Proteins, Oncogenic Transcription Factors oncogene proteins v-ets v-Spi-1 protein, Friend spleen focus-forming virus Globins DNA
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Galson D L
Center for Cancer Research, Massachusetts Institute of Technology, Cambridge 02139.
Hensold J O
Bishop T R
Schalling M
D'Andrea A D
Jones C
Auron P E
Housman D E
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Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
Published
1993-05-00
Pages
2929-41
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC359686
Subset
IM
Grants
NCI NIH HHS · CA-18724 · United States
NIDDK NIH HHS · DK-39888 · United States
NCI NIH HHS · P30-CA-43703 · United States
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