PU.1 can Participate in an Active Enhancer Complex without its Transcriptional Activation Domain

The transcription factor PU.1 is necessary for the development of multiple hematopoietic lineages and contributes to the activity of the immunoglobulin κ 3′ enhancer. A variety of proteins bind to the 3′ enhancer (PU.1, PIP, ATF1, CREM, c-Fos, c-Jun, and E2A), but the mechanism of 3′-enhancer activi...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 1997-01, Vol.94 (1), p.127-132
Main Authors: Jagan M. R. Pongubala, Atchison, Michael L.
Format: Article
Language:English
Subjects:
B lymphocytes
Binding sites
Biological Sciences
Carrier proteins
DNA
DNA-Binding Proteins - metabolism
DNA-Binding Proteins - pharmacology
Drug Synergism
Enhancer Elements, Genetic
Immunoglobulin kappa-Chains - genetics
Interferon Regulatory Factors
Models, Genetic
NIH 3T3 cells
Nucleoproteins
Plasmids
Protein Binding
Proto-Oncogene Proteins - metabolism
Proto-Oncogene Proteins - pharmacology
Trans-Activators - metabolism
Trans-Activators - pharmacology
Transactivation
Transcription factors
Transcription Factors - metabolism
Transcription Factors - pharmacology
Transcription, Genetic
Transcriptional activation
Transfection
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Summary:The transcription factor PU.1 is necessary for the development of multiple hematopoietic lineages and contributes to the activity of the immunoglobulin κ 3′ enhancer. A variety of proteins bind to the 3′ enhancer (PU.1, PIP, ATF1, CREM, c-Fos, c-Jun, and E2A), but the mechanism of 3′-enhancer activity and the proteins necessary for its activity are presently unclear. We show here that PU.1 participates with other transcription factors in forming a higher-order complex with 3′-enhancer DNA sequences. Each protein is necessary for formation of this complex. Individually, transcription factors that bind to the 3′ enhancer do not appreciably stimulate transcription in a cell type in which the 3′ enhancer is normally silent (NIH 3T3). However, mixture of multiple transcription factors (PU.1, PIP, c-Fos, and c-Jun) can greatly activate the enhancer. PU.1 is necessary for maximal enhancer activity, but mutants of PU.1 that lack the transcriptional activation domain are nearly as efficient at stimulating enhancer activity as the wild-type PU.1 protein. PU.1 apparently can activate transcription by playing an architectural role in interactions with other transcription factors.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.94.1.127