| Summary: | <p>Abstract</p> <p>Background</p> <p>Chromosomal aberrations of <it>BCL11A </it>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.</p> <p>Results</p> <p>Alternative pre-mRNA splicing of <it>BCL11A </it>produces multiple isoforms sharing a common N-terminus. The most abundant isoform we have identified in human lymphoid samples is <it>BCL11A-XL</it>, 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 <it>in vitro</it>, 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.</p> <p>Conclusion</p> <p>We propose that the conserved N-terminus of BCL11A defines a superfamily of C2HC zinc-finger transcription factors involved in hematopoietic malignancies.</p>
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