Functional studies of BCL11A: characterization of the conserved BCL11A-XL splice variant and its interaction with BCL6 in nuclear paraspeckles of germinal center B cells.
BACKGROUND: Chromosomal aberrations of BCL11A at 2p16.1 have been reported in a variety of B-cell malignancies and its deficiency in mice leads to a profound block in B-cell development. RESULTS: Alternative pre-mRNA splicing of BCL11A produces multiple isoforms sharing a common N-terminus. The most...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
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2006
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| _version_ | 1826257857507491840 |
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| author | Liu, H Ippolito, G Wall, J Niu, T Probst, L Lee, B Pulford, K Banham, A Stockwin, L Shaffer, A Staudt, L Das, C Dyer, M Tucker, P |
| author_facet | Liu, H Ippolito, G Wall, J Niu, T Probst, L Lee, B Pulford, K Banham, A Stockwin, L Shaffer, A Staudt, L Das, C Dyer, M Tucker, P |
| author_sort | Liu, H |
| collection | OXFORD |
| description | BACKGROUND: Chromosomal aberrations of BCL11A at 2p16.1 have been reported in a variety of B-cell malignancies and its deficiency in mice leads to a profound block in B-cell development. RESULTS: Alternative pre-mRNA splicing of BCL11A produces multiple isoforms sharing a common N-terminus. The most abundant isoform we have identified in human lymphoid samples is BCL11A-XL, the longest transcript produced at this locus, and here we report the conservation of this major isoform and its functional characterization. We show that BCL11A-XL is a DNA-sequence-specific transcriptional repressor that associates with itself and with other BCL11A isoforms, as well as with the BCL6 proto-oncogene. Western blot data for BCL11A-XL expression coupled with data previously published for BCL6 indicates that these genes are expressed abundantly in germinal-center-derived B cells but that expression is extinguished upon terminal differentiation to the plasma cell stage. Although BCL11A-XL/BCL6 interaction can modulate BCL6 DNA binding in vitro, their heteromeric association does not alter the homomeric transcriptional properties of either on model reporter activity. BCL11A-XL partitions into the nuclear matrix and colocalizes with BCL6 in nuclear paraspeckles. CONCLUSION: We propose that the conserved N-terminus of BCL11A defines a superfamily of C2HC zinc-finger transcription factors involved in hematopoietic malignancies. |
| first_indexed | 2024-03-06T18:24:48Z |
| format | Journal article |
| id | oxford-uuid:079342e1-cc35-405b-8c04-aa81bd73cf33 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T18:24:48Z |
| publishDate | 2006 |
| record_format | dspace |
| spelling | oxford-uuid:079342e1-cc35-405b-8c04-aa81bd73cf332022-03-26T09:08:20ZFunctional studies of BCL11A: characterization of the conserved BCL11A-XL splice variant and its interaction with BCL6 in nuclear paraspeckles of germinal center B cells.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:079342e1-cc35-405b-8c04-aa81bd73cf33EnglishSymplectic Elements at Oxford2006Liu, HIppolito, GWall, JNiu, TProbst, LLee, BPulford, KBanham, AStockwin, LShaffer, AStaudt, LDas, CDyer, MTucker, PBACKGROUND: Chromosomal aberrations of BCL11A at 2p16.1 have been reported in a variety of B-cell malignancies and its deficiency in mice leads to a profound block in B-cell development. RESULTS: Alternative pre-mRNA splicing of BCL11A produces multiple isoforms sharing a common N-terminus. The most abundant isoform we have identified in human lymphoid samples is BCL11A-XL, the longest transcript produced at this locus, and here we report the conservation of this major isoform and its functional characterization. We show that BCL11A-XL is a DNA-sequence-specific transcriptional repressor that associates with itself and with other BCL11A isoforms, as well as with the BCL6 proto-oncogene. Western blot data for BCL11A-XL expression coupled with data previously published for BCL6 indicates that these genes are expressed abundantly in germinal-center-derived B cells but that expression is extinguished upon terminal differentiation to the plasma cell stage. Although BCL11A-XL/BCL6 interaction can modulate BCL6 DNA binding in vitro, their heteromeric association does not alter the homomeric transcriptional properties of either on model reporter activity. BCL11A-XL partitions into the nuclear matrix and colocalizes with BCL6 in nuclear paraspeckles. CONCLUSION: We propose that the conserved N-terminus of BCL11A defines a superfamily of C2HC zinc-finger transcription factors involved in hematopoietic malignancies. |
| spellingShingle | Liu, H Ippolito, G Wall, J Niu, T Probst, L Lee, B Pulford, K Banham, A Stockwin, L Shaffer, A Staudt, L Das, C Dyer, M Tucker, P Functional studies of BCL11A: characterization of the conserved BCL11A-XL splice variant and its interaction with BCL6 in nuclear paraspeckles of germinal center B cells. |
| title | Functional studies of BCL11A: characterization of the conserved BCL11A-XL splice variant and its interaction with BCL6 in nuclear paraspeckles of germinal center B cells. |
| title_full | Functional studies of BCL11A: characterization of the conserved BCL11A-XL splice variant and its interaction with BCL6 in nuclear paraspeckles of germinal center B cells. |
| title_fullStr | Functional studies of BCL11A: characterization of the conserved BCL11A-XL splice variant and its interaction with BCL6 in nuclear paraspeckles of germinal center B cells. |
| title_full_unstemmed | Functional studies of BCL11A: characterization of the conserved BCL11A-XL splice variant and its interaction with BCL6 in nuclear paraspeckles of germinal center B cells. |
| title_short | Functional studies of BCL11A: characterization of the conserved BCL11A-XL splice variant and its interaction with BCL6 in nuclear paraspeckles of germinal center B cells. |
| title_sort | functional studies of bcl11a characterization of the conserved bcl11a xl splice variant and its interaction with bcl6 in nuclear paraspeckles of germinal center b cells |
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