scholarly journals The BCL11A Transcription Factor Directly Activates RAG Gene Expression and V(D)J Recombination

2013 ◽  
Vol 33 (9) ◽  
pp. 1768-1781 ◽  
Author(s):  
Baeck-seung Lee ◽  
Joseph D. Dekker ◽  
Bum-kyu Lee ◽  
Vishwanath R. Iyer ◽  
Barry P. Sleckman ◽  
...  
Keyword(s):  
Transcription Factor ◽  
B Cells ◽  
B Cell ◽  
Cell Fate ◽  
B Cell Development ◽  
Receptor Expression ◽  
Molecular Function ◽  
Cell Fate Specification ◽  
Fate Specification ◽  
Recombination Activating Gene

Recombination-activating gene 1 protein (RAG1) and RAG2 are critical enzymes for initiating variable-diversity-joining (VDJ) segment recombination, an essential process for antigen receptor expression and lymphocyte development. The transcription factor BCL11A is required for B cell development, but its molecular function(s) in B cell fate specification and commitment is unknown. We show here that the major B cell isoform, BCL11A-XL, binds the RAG1 promoter and Erag enhancer to activate RAG1 and RAG2 transcription in pre-B cells. We employed BCL11A overexpression with recombination substrates in a cultured pre-B cell line as well as Cre recombinase-mediated Bcl11a lox/lox deletion in explanted murine pre-B cells to demonstrate direct consequences of BCL11A/RAG modulation on V(D)J recombination. We conclude that BCL11A is a critical component of a transcriptional network that regulates B cell fate by controlling V(D)J recombination.

scholarly journals Corrected and Republished from: BCL11A Is a Critical Component of a Transcriptional Network That Activates RAG Expression and V(D)J Recombination

2017 ◽  
Vol 38 (1) ◽  
Author(s):  
Baeck-Seung Lee ◽  
Bum-Kyu Lee ◽  
Vishwanath R. Iyer ◽  
Barry P. Sleckman ◽  
Arthur L. Shaffer ◽  
...  
Keyword(s):  
B Cell ◽  
Cell Fate ◽  
Plasmacytoid Dendritic Cell ◽  
Transcriptional Network ◽  
Receptor Expression ◽  
Molecular Function ◽  
Cell Fate Specification ◽  
Critical Component ◽  
Rag2 Gene ◽  
Recombination Activating Gene

ABSTRACT Recombination activating gene 1 (RAG1) and RAG2 are critical enzymes for initiating variable-diversity-joining [V(D)J] segment recombination, an essential process for antigen receptor expression and lymphocyte development. The BCL11A transcription factor is required for B cell and plasmacytoid dendritic cell (pDC) development, but its molecular function(s) in early B cell fate specification and commitment is unknown. We show here that the major B cell isoform, BCL11A-XL, binds directly to the RAG1 promoter as well as directly to regulatory regions of transcription factors previously implicated in both B cell and pDC development to activate RAG1 and RAG2 gene transcription in pro- and pre-B cells. We employed BCL11A overexpression with recombination substrates to demonstrate direct consequences of BCL11A/RAG modulation on V(D)J recombination. We conclude that BCL11A is a critical component of a transcriptional network that regulates B cell fate by controlling V(D)J recombination.

scholarly journals IL-7 receptor signaling is necessary for stage transition in adult B cell development through up-regulation of EBF

2005 ◽  
Vol 201 (8) ◽  
pp. 1197-1203 ◽  
Author(s):  
Kazu Kikuchi ◽  
Anne Y. Lai ◽  
Chia-Lin Hsu ◽  
Motonari Kondo
Keyword(s):  
Transcription Factor ◽  
B Cells ◽  
B Cell ◽  
Target Genes ◽  
Cell Development ◽  
B Cell Development ◽  
Receptor Signaling ◽  
Cell Stage ◽  
Transcription Factor Network ◽  
Stage Transition

Cytokine receptor signals have been suggested to stimulate cell differentiation during hemato/lymphopoiesis. Such action, however, has not been clearly demonstrated. Here, we show that adult B cell development in IL-7−/− and IL-7Rα2/− mice is arrested at the pre–pro-B cell stage due to insufficient expression of the B cell–specific transcription factor EBF and its target genes, which form a transcription factor network in determining B lineage specification. EBF expression is restored in IL-7−/− pre–pro-B cells upon IL-7 stimulation or in IL-7Rα−/− pre–pro-B cells by activation of STAT5, a major signaling molecule downstream of the IL-7R signaling pathway. Furthermore, enforced EBF expression partially rescues B cell development in IL-7Rα−/− mice. Thus, IL-7 receptor signaling is a participant in the formation of the transcription factor network during B lymphopoiesis by up-regulating EBF, allowing stage transition from the pre–pro-B to further maturational stages.

scholarly journals Regulation of B cell fate specification and V H gene rearrangements by Ikaros

2008 ◽  
Vol 22 (S1) ◽  
Author(s):  
Damien REYNAUD ◽  
Karen REDDY ◽  
Hilde SCHJERVEN ◽  
Chauncey SPOONER ◽  
Eric BERTOLINO ◽  
...  
Keyword(s):  
B Cell ◽  
Cell Fate ◽  
Gene Rearrangements ◽  
Cell Fate Specification ◽  
Fate Specification ◽  
H Gene

scholarly journals Developmental clock and mechanism of de novo polarization of the mouse embryo

Science ◽  
2020 ◽  
Vol 370 (6522) ◽  
pp. eabd2703
Author(s):  
Meng Zhu ◽  
Jake Cornwall-Scoones ◽  
Peizhe Wang ◽  
Charlotte E. Handford ◽  
Jie Na ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Cell Fate ◽  
De Novo ◽  
Cell Fate Specification ◽  
Mouse Development ◽  
Fate Specification ◽  
Apical Domain ◽  
Transcription Factor 4 ◽  
Genome Activation ◽  
Zygotic Genome

Embryo polarization is critical for mouse development; however, neither the regulatory clock nor the molecular trigger that it activates is known. Here, we show that the embryo polarization clock reflects the onset of zygotic genome activation, and we identify three factors required to trigger polarization. Advancing the timing of transcription factor AP-2 gamma (Tfap2c) and TEA domain transcription factor 4 (Tead4) expression in the presence of activated Ras homolog family member A (RhoA) induces precocious polarization as well as subsequent cell fate specification and morphogenesis. Tfap2c and Tead4 induce expression of actin regulators that control the recruitment of apical proteins on the membrane, whereas RhoA regulates their lateral mobility, allowing the emergence of the apical domain. Thus, Tfap2c, Tead4, and RhoA are regulators for the onset of polarization and cell fate segregation in the mouse.

Stem Cell Fate Specification: Role of Master Regulatory Switch Transcription Factor PU.1 in Differential Hematopoiesis

2005 ◽  
Vol 14 (2) ◽  
pp. 140-152 ◽  
Author(s):  
Gurudutta U. Gangenahalli ◽  
Pallavi Gupta ◽  
Daman Saluja ◽  
Yogesh K. Verma ◽  
Vimal Kishore ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Stem Cell ◽  
Cell Fate ◽  
Cell Fate Specification ◽  
Stem Cell Fate ◽  
Fate Specification

scholarly journals The B29 (Immunoglobulin β-Chain) Gene Is a Genetic Target for Early B-Cell Factor

1999 ◽  
Vol 19 (1) ◽  
pp. 392-401 ◽  
Author(s):  
Peter Åkerblad ◽  
Maria Rosberg ◽  
Tomas Leanderson ◽  
Mikael Sigvardsson
Keyword(s):  
Transcription Factor ◽  
B Cells ◽  
B Cell ◽  
B Lymphocyte ◽  
Ectopic Expression ◽  
Cell Receptor ◽  
Cell Development ◽  
B Cell Development ◽  
Chain Gene ◽  
Early B Cell Factor

ABSTRACT Early B-cell factor (EBF) is a transcription factor suggested as essential for early B-lymphocyte development by findings in mice where the coding gene has been inactivated by homologous disruption. This makes the identification of genetic targets for this transcription factor pertinent for the understanding of early B-cell development. The lack of B29 transcripts, coding for the β subunit of the B-cell receptor complex, in pro-B cells from EBF-deficient mice suggested that B29 might be a genetic target for EBF. We here present data suggesting that EBF interacts with three independent sites within the mouse B29 promoter. Furthermore, ectopic expression of EBF in HeLa cells activated a B29promoter-controlled reporter construct 13-fold and induced a low level of expression from the endogenous B29 gene. Finally, mutations in the EBF binding sites diminished B29 promoter activity in pre-B cells while the same mutations did not have as striking an effect on the promoter function in B-cell lines of later differentiation stages. These data suggest that the B29gene is a genetic target for EBF in early B-cell development.

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