Octamer-binding proteins from B or HeLa cells stimulate transcription of the immunoglobulin heavy-chain promoter in vitro.
The B-cell-type specificity of the immunoglobulin (Ig) heavy-chain and light-chain promoters is mediated by an octanucleotide (OCTA) element, ATGCAAAT, that is also a functional component of other RNA polymerase II promoters, such as snRNA and histone H2B promoters. Two nuclear proteins that bind specifically and with high affinity to the OCTA element have been identified. NF-A1 is present in a variety of cell types, whereas the presence of NF-A2 is essentially confined to B cells, leading to the hypothesis that NF-A2 activates cell-type-specific transcription of the Ig promoter and NF-A1 mediates the other responses of the OCTA element. Extracts of the B-cell line, BJA-B, contain high levels of NF-A2 and specifically transcribe Ig promoters. In contrast, extracts from HeLa cells transcribed the Ig promoter poorly. Surprisingly, addition of either affinity-enriched NF-A2 or NF-A1 to either a HeLa extract or a partially purified reaction system specifically stimulates the Ig promoter. This suggests that the constitutive OCTA-binding factor NF-A1 can activate transcription of the Ig promoter and that B-cell-specific transcription of this promoter, at least in vitro, is partially due to a quantitative difference in the amount of OCTA-binding protein. Because NF-A1 can stimulate Ig transcription, the inability of this factor to activate in vivo the Ig promoter to the same degree as the snRNA promoters probably reflects a difference in the context of the OCTA element in these two types of promoters.
LeBowitz
J H
JH
Center for Cancer Research, Massachusetts Institute of Technology, Cambridge 02139.
Kobayashi
T
T
Staudt
L
L
Baltimore
D
D
Sharp
P A
PA
D001402:B-Lymphocytes / Q000032:analysis / Q000502:physiology; D001483:Base Sequence; D002457:Cell Extracts / Q000494:pharmacology; D002467:Cell Nucleus / Q000502:physiology; D002846:Chromatography, Affinity; D015342:DNA Probes; D004268:DNA-Binding Proteins / Q000502:physiology*; D005786:Gene Expression Regulation; D005803:Genes, Immunoglobulin; D006367:HeLa Cells / Q000032:analysis / Q000502:physiology; D006801:Humans; D010957:Plasmids; D011401:Promoter Regions, Genetic; D014157:Transcription Factors / Q000502:physiology*
D002457:Cell Extracts; D015342:DNA Probes; D004268:DNA-Binding Proteins; D014157:Transcription Factors