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Published on: May 27, 2016
Dependence of BSAP repressor and activator functions on BSAP concentration
J J Wallin1, E R Gackstetter, M E Koshland
1Immunology Division, Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA.
Science (New York, N.Y.)
|April 16, 1998
Summary
During B cell immune responses, the transcription factor BSAP selectively uses activator functions. Its repressor functions are relieved via a concentration-dependent mechanism, with motif context, not binding affinity, determining BSAP
Area of Science:
- Immunology
- Molecular Biology
- Transcription Factor Regulation
Background:
- B cell immune responses involve intricate regulation of gene expression.
- The transcription factor BSAP (also known as Pax5) plays a crucial role in B cell development and function.
- Understanding how BSAP's dual activator and repressor functions are controlled is key to deciphering immune responses.
Purpose of the Study:
- To investigate the regulatory mechanisms governing the selective targeting of BSAP's activator and repressor functions during B cell immune responses.
- To determine the relative importance of binding affinity versus DNA motif context in dictating BSAP's functional output.
Main Methods:
- Analysis of BSAP binding affinities to its activator and repressor motifs.
- Experimental manipulation involving the exchange of activator and repressor motifs within regulatory elements.
- Assessment of BSAP's functional consequences (activation vs. repression) following motif context alteration.
Main Results:
- BSAP maintains activator functions while its repressor functions are selectively relieved during immune responses.
- A concentration-dependent mechanism was identified, where BSAP activator motifs exhibit a 20-fold higher binding affinity than repressor motifs.
- Exchanging activator and repressor motifs demonstrated that the surrounding DNA context, not just binding affinity, dictates whether BSAP acts as an activator or repressor.
Conclusions:
- The functional outcome of BSAP is primarily determined by the specific DNA sequence context of its binding sites, overriding simple binding affinity differences.
- This context-dependent regulation provides a sophisticated mechanism for fine-tuning B cell gene expression during immune activation.
- The findings highlight a novel layer of control in transcription factor activity, crucial for adaptive immunity.
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