Liu Hui, Ippolito Gregory C, Wall Jason K, Niu Teresa, Probst Loren, Lee Baeck-Seung, Pulford Karen, Banham Alison H, Stockwin Luke, Shaffer Arthur L, Staudt Louis M, Das Chhaya, Dyer Martin J S, Tucker Philip W
Section of Molecular Genetics and Microbiology and Institute for Cellular and Molecular Biology, 1 University Station, A5000, University of Texas, Austin, Texas 78712, USA.
Mol Cancer. 2006 May 16;5:18. doi: 10.1186/1476-4598-5-18.
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.
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.
We propose that the conserved N-terminus of BCL11A defines a superfamily of C2HC zinc-finger transcription factors involved in hematopoietic malignancies.
2p16.1处BCL11A的染色体畸变已在多种B细胞恶性肿瘤中被报道，并且其在小鼠中的缺陷会导致B细胞发育的严重阻滞。
BCL11A的可变前体mRNA剪接产生了多个共享共同N端的异构体。我们在人类淋巴样本中鉴定出的最丰富的异构体是BCL11A-XL，即该基因座产生的最长转录本，在此我们报道了这种主要异构体的保守性及其功能特征。我们表明BCL11A-XL是一种DNA序列特异性转录抑制因子，它能与自身、其他BCL11A异构体以及BCL6原癌基因结合。BCL11A-XL表达的蛋白质印迹数据与先前发表的BCL6数据表明，这些基因在生发中心来源的B细胞中大量表达，但在终末分化为浆细胞阶段时表达消失。尽管BCL11A-XL/BCL6相互作用在体外可调节BCL6与DNA的结合，但它们的异源二聚体结合并不会改变两者在模型报告基因活性上的同源转录特性。BCL11A-XL定位于核基质，并与BCL6在核副斑点中共定位。
我们提出，BCL11A保守的N端定义了一个参与造血系统恶性肿瘤的C2HC锌指转录因子超家族。
