| First Author | Banerjee A | Year | 2013 |
| Journal | Immunity | Volume | 38 |
| Issue | 5 | Pages | 930-42 |
| PubMed ID | 23684985 | Mgi Jnum | J:203150 |
| Mgi Id | MGI:5525041 | Doi | 10.1016/j.immuni.2013.01.014 |
| Citation | Banerjee A, et al. (2013) Transcriptional repression of Gata3 is essential for early B cell commitment. Immunity 38(5):930-42 |
| abstractText | The mechanisms underlying the silencing of alternative fate potentials in very early B cell precursors remain unclear. Using gain- and loss-of-function approaches together with a synthetic Zinc-finger polypeptide (6ZFP) engineered to prevent transcription factor binding to a defined cis element, we show that the transcription factor EBF1 promotes B cell lineage commitment by directly repressing expression of the T-cell-lineage-requisite Gata3 gene. Ebf1-deficient lymphoid progenitors exhibited increased T cell lineage potential and elevated Gata3 transcript expression, whereas enforced EBF1 expression inhibited T cell differentiation and caused rapid loss of Gata3 mRNA. Notably, 6ZFP-mediated perturbation of EBF1 binding to a Gata3 regulatory region restored Gata3 expression, abrogated EBF1-driven suppression of T cell differentiation, and prevented B cell differentiation via a GATA3-dependent mechanism. Furthermore, EBF1 binding to Gata3 regulatory sites induced repressive histone modifications across this region. These data identify a transcriptional circuit critical for B cell lineage commitment. |
