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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.

Original publication

DOI

10.1186/1476-4598-5-18

Type

Journal article

Journal

Mol Cancer

Publication Date

16/05/2006

Volume

5

Keywords

Alternative Splicing, Animals, Blotting, Western, COS Cells, Carrier Proteins, Cell Differentiation, Cell Line, Cell Line, Tumor, Cercopithecus aethiops, Gene Expression Profiling, Germinal Center, HeLa Cells, Humans, Immunoprecipitation, Lymphoma, B-Cell, Mice, Microscopy, Fluorescence, NIH 3T3 Cells, Nuclear Matrix, Nuclear Proteins, Protein Isoforms, Proto-Oncogene Proteins, Proto-Oncogene Proteins c-bcl-6