PMID:15454082

Citation	Fujita, N, Jaye, DL, Geigerman, C, Akyildiz, A, Mooney, MR, Boss, JM and Wade, PA (2004) MTA3 and the Mi-2/NuRD complex regulate cell fate during B lymphocyte differentiation. Cell 119:75-86
Abstract	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.
Links	PubMed Online version:10.1016/j.cell.2004.09.014
Keywords	Acetylation; Adenosine Triphosphatases/genetics; Adenosine Triphosphatases/metabolism; Antigens, Surface/genetics; Antigens, Surface/metabolism; Autoantigens/genetics; Autoantigens/metabolism; B-Lymphocytes/immunology; B-Lymphocytes/metabolism; Cell Differentiation/genetics; Cell Differentiation/immunology; Cell Lineage/genetics; Cell Lineage/immunology; DNA Helicases/genetics; DNA Helicases/metabolism; DNA-Binding Proteins/genetics; DNA-Binding Proteins/metabolism; Genes, Regulator/genetics; HeLa Cells; Histone Deacetylases/genetics; Histone Deacetylases/metabolism; Humans; Lymphocyte Activation/genetics; Mi-2 Nucleosome Remodeling and Deacetylase Complex; Neoplasm Proteins/genetics; Neoplasm Proteins/metabolism; Plasma Cells/immunology; Plasma Cells/metabolism; Proto-Oncogene Proteins/genetics; Proto-Oncogene Proteins/metabolism; Proto-Oncogene Proteins c-bcl-6; RNA Interference; Repressor Proteins/genetics; Repressor Proteins/metabolism; Transcription Factors/genetics; Transcription Factors/metabolism; Transcriptional Activation/genetics
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
HUMAN:MTA3		GO:0045892: negative regulation of transcription, DNA-dependent	ECO:0000315:		P		Figure 3D shows that repression, driven by the central region of BCL-6, was affected by MTA3 depletion. It can be concluded that MTA3 contributes to transcriptional repression by Gal4-BCL-6 through interaction with a transcriptional repression domain in the central region of BCL-6.	complete CACAO 7304
HUMAN:MTA3	involved_in	GO:0045892: negative regulation of transcription, DNA-templated	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete

References

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