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ETS protein-dependent accessibility changes at the immunoglobulin mu heavy chain enhancer
B S Nikolajczyk1, J A Sanchez, R Sen
1Rosenstiel Research Center and Department of Biology, Brandeis University, Waltham, Massachusetts 02454, USA.
Immunity
|August 6, 1999
Summary
The study reveals how PU.1 binding to the immunoglobulin heavy chain enhancer increases chromatin accessibility. This mechanism is crucial for initiating heavy chain gene expression during development.
Area of Science:
- Immunology
- Molecular Biology
- Genetics
Background:
- Antigen-receptor gene enhancers regulate V(D)J recombination during development.
- Chromatin accessibility is critical for developmental stage-specific gene activation.
Purpose of the Study:
- To investigate the mechanisms controlling immunoglobulin mu heavy chain gene enhancer-dependent chromatin accessibility.
- To elucidate the role of transcription factors Ets-1 and PU.1 in this process.
Main Methods:
- In vitro assays using plasmids with mu enhancer sequences.
- In vivo analyses in pro-T cells and NIH 3T3 cells.
- Assessing chromatin accessibility using restriction enzyme digestion and monitoring sterile I mu transcripts.
Main Results:
- Binding of Ets-1 or PU.1 to mu enhancer plasmids increased chromatin accessibility in vitro.
- PU.1 expression in cells induced sterile I mu transcripts and enhanced accessibility of the endogenous mu enhancer.
- These factors directly influence the accessibility of the immunoglobulin heavy chain locus.
Conclusions:
- PU.1 plays a key role in increasing chromatin accessibility at the immunoglobulin heavy chain locus.
- This accessibility is a prerequisite for initiating heavy chain gene expression.
- The findings provide insight into the regulation of V(D)J recombination and B-cell development.