MTA3 and the Mi-2/NuRD complex regulate cell fate during B lymphocyte differentiation.

The transcriptional repressor BCL-6 regulates B lymphocyte cell fate during the germinal center reaction by preventing terminal differentiation of B lymphocytes into plasma cells until appropriate signals are received. Here, we report a cofactor, MTA3, a cell type-specific subunit of the corepressor complex Mi-2/NuRD, for BCL-6-dependent cell fate determination. MTA3 ...
is expressed in the same pattern in germinal centers as BCL-6. BCL-6 physically interacts with Mi-2/NuRD and this interaction is sensitive to BCL-6 acetylation status. Depletion of MTA3 by RNAi impairs BCL-6-dependent repression and alters the cell-specific transcriptional pattern characteristic of the B lymphocyte. Remarkably, exogenous expression of BCL-6 in a plasma cell line leads, in an MTA3-dependent manner, to repression of plasma cell-specific transcripts, reactivation of the B cell transcriptional program, expression of B lymphocyte cell surface markers, and reprogramming of cell fate.
Mesh Terms:
Acetylation, Adenosine Triphosphatases, Antigens, Surface, Autoantigens, B-Lymphocytes, Cell Differentiation, Cell Lineage, DNA Helicases, DNA-Binding Proteins, Genes, Regulator, Hela Cells, Histone Deacetylases, Humans, Lymphocyte Activation, Mi-2 Nucleosome Remodeling and Deacetylase Complex, Neoplasm Proteins, Plasma Cells, Proto-Oncogene Proteins, Proto-Oncogene Proteins c-bcl-6, RNA Interference, Repressor Proteins, Transcription Factors, Transcriptional Activation
Cell
Date: Oct. 01, 2004
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