Positive autoregulation of c-myb expression via Myb binding sites in the 5 prime flanking region of the human c-myb gene

Journal Article · Sun Dec 01 04:00:00 EST 1991 · Molecular and Cellular Biology; (United States)

DOI:https://doi.org/10.1128/MCB.11.12.6166· OSTI ID:5144580

Nicolaides, N C; Gualdi, R; Casadevall, C; Manzella, L; Calabretta, B ^[1]

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1. Thomas Jefferson Univ., Philadelphia, PA (United States)

The nuclear proto-oncogene c-myb is preferentially expressed in lymphohematopoietic cells, in which it plays an important role in the processes of differentiation and proliferation. The mechanism(s) that regulates c-myb expression is not fully understood, although in mouse cells a regulatory mechanism involves a transcriptional block in the first intron. To analyze the contribution of the 5{prime} flanking sequences in regulating the expression of the human c-myb gene, the authors isolated a genomic clone containing extensive 5{prime} flanking sequences, the first exon, and a large portion of the first intron. Sequence analysis of a subcloned 1.3-kb BamHI insert corresponding to 687 nucleotides of the 5{prime} flanking sequences, the entire first exon, and 300 nucleotides of the first intron revealed the presence of closely spaced putative Myb binding sites within a segment extending from nucleotides {minus}616 to {minus}575 upstream from the cap site. A 165-bp segment containing these putative Myb binding sites was linked to a human thymidine kinase (TK) cDAN driven by a low-activity proliferating cell nuclear antigen promoter and cotransfected into TK{sup {minus}} ts13 cells with a plasmid in which a full-length human c-myb cDNA is driven by the early simian virus 40 promoter; Myb inducibility of TK mRNA expression was observed both in transient expression assays and in stable transformants. These data suggest that human c-myb maintains high levels of Myb protein in cells that require this gene product for proliferation and/or differentiation by an autoregulatory mechanism involving Myb binding sites in the 5{prime} flanking region.

• OSTI ID: 5144580
• Journal Information: Molecular and Cellular Biology; (United States), Journal Name: Molecular and Cellular Biology; (United States) Vol. 11:12; ISSN MCEBD; ISSN 0270-7306
• Country of Publication: United States
• Language: English

Related Subjects

550200* -- Biochemistry
59 BASIC BIOLOGICAL SCIENCES
ANIMAL CELLS
ANIMALS
AZINES
BODY
CELL DIFFERENTIATION
CELL PROLIFERATION
DNA
ENZYMES
GENE REGULATION
GENES
HEMATOPOIETIC SYSTEM
HETEROCYCLIC COMPOUNDS
MAMMALS
MAN
NUCLEIC ACIDS
NUCLEOSIDES
NUCLEOTIDES
ONCOGENES
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
PHOSPHORUS-GROUP TRANSFERASES
PHOSPHOTRANSFERASES
PRIMATES
PROTEINS
PYRIMIDINES
RECOMBINANT DNA
RIBOSIDES
THYMIDINE
TRANSFERASES
TUMOR CELLS
VERTEBRATES