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Prediction and Validation of Gene Regulatory Elements Activated During Retinoic Acid Induced Embryonic Stem Cell Differentiation
Published on: June 21, 2016
Regulatory events in early and late B-cell differentiation
Kristen Johnson1, Miriam Shapiro-Shelef, Chainarong Tunyaplin
1Department of Microbiology, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA.
Molecular Immunology
|April 15, 2005
Summary
Pax5 controls B cell development by removing repressive chromatin marks. Blimp-1 drives terminal differentiation into antibody-secreting plasma cells, with its regulation involving Bcl-6 and NF-kappaB signaling.
Area of Science:
- Immunology
- Molecular Biology
- Developmental Biology
Background:
- B lymphocyte lineage commitment relies on the transcription factor Pax5.
- Immunoglobulin (Ig) heavy chain V(H)-to-DJ recombination initiates during B cell commitment.
- Heterochromatic histone H3 lysine 9 methylation marks the Ig V(H) region in progenitors and non-B cells.
Purpose of the Study:
- To investigate the role of Pax5 in removing heterochromatic marks at the Ig V(H) locus.
- To elucidate the function of the transcriptional repressor Blimp-1 in B cell terminal differentiation.
- To understand the regulatory mechanisms controlling Blimp-1 expression.
Main Methods:
- Utilizing genetically altered mouse models.
- Analyzing chromatin modifications, specifically histone methylation.
- Investigating gene regulation through transcription factor interactions.
Main Results:
- Pax5 is essential and sufficient for the removal of H3K9me heterochromatin marks in B cells.
- Blimp-1 is crucial for B cell differentiation into memory and antibody-secreting plasma cells.
- Bcl-6 directly represses Blimp-1, while NF-kappaB activates it downstream of toll-like receptor signaling.
Conclusions:
- Pax5 orchestrates B cell identity by epigenetic reprogramming of the Ig locus.
- Blimp-1 acts as a key switch for terminal B cell differentiation.
- The intricate regulation of Blimp-1 by Bcl-6 and NF-kappaB fine-tunes plasma cell development and function.
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