Transcriptional repression of Gata3 is essential for early B cell commitment.
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...
| المؤلفون الرئيسيون: | , , , , |
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| التنسيق: | Journal article |
| اللغة: | English |
| منشور في: |
2013
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| _version_ | 1826300099784867840 |
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| author | Banerjee, A Northrup, D Boukarabila, H Jacobsen, SE Allman, D |
| author_facet | Banerjee, A Northrup, D Boukarabila, H Jacobsen, SE Allman, D |
| author_sort | Banerjee, A |
| collection | OXFORD |
| description | 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. |
| first_indexed | 2024-03-07T05:12:00Z |
| format | Journal article |
| id | oxford-uuid:dbdfeee9-7e93-4eaa-8c21-16f26f2d0c87 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T05:12:00Z |
| publishDate | 2013 |
| record_format | dspace |
| spelling | oxford-uuid:dbdfeee9-7e93-4eaa-8c21-16f26f2d0c872022-03-27T09:13:44ZTranscriptional repression of Gata3 is essential for early B cell commitment.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:dbdfeee9-7e93-4eaa-8c21-16f26f2d0c87EnglishSymplectic Elements at Oxford2013Banerjee, ANorthrup, DBoukarabila, HJacobsen, SEAllman, DThe 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. |
| spellingShingle | Banerjee, A Northrup, D Boukarabila, H Jacobsen, SE Allman, D Transcriptional repression of Gata3 is essential for early B cell commitment. |
| title | Transcriptional repression of Gata3 is essential for early B cell commitment. |
| title_full | Transcriptional repression of Gata3 is essential for early B cell commitment. |
| title_fullStr | Transcriptional repression of Gata3 is essential for early B cell commitment. |
| title_full_unstemmed | Transcriptional repression of Gata3 is essential for early B cell commitment. |
| title_short | Transcriptional repression of Gata3 is essential for early B cell commitment. |
| title_sort | transcriptional repression of gata3 is essential for early b cell commitment |
| work_keys_str_mv | AT banerjeea transcriptionalrepressionofgata3isessentialforearlybcellcommitment AT northrupd transcriptionalrepressionofgata3isessentialforearlybcellcommitment AT boukarabilah transcriptionalrepressionofgata3isessentialforearlybcellcommitment AT jacobsense transcriptionalrepressionofgata3isessentialforearlybcellcommitment AT allmand transcriptionalrepressionofgata3isessentialforearlybcellcommitment |