Accumulating studies indicate that the nuclear matrix provides a dynamic structural support for various biological reactions inside of nuclei such as DNA replication, RNA transcription, and RNA splicing. Pax5 is an important regulator for B lineage cell development, which controls the B lineage specific gene expression program involving hundreds of positive and negative target genes. Here, we show that majority of the endogenous Pax5 proteins in human and murine B lineage cells are associated with the nuclear matrix, where they occupy the centers for transcription on the nuclear matrix as indicated by co-localization with the RNA polymerase II or the TATA box binding protein (TBP). Detailed analyses identified that two different domains of Pax5 are required for its association with the nuclear matrix. Interestingly, lysine 67, 87, and 89 residues within the PRD domain of Pax5 are essential for its association with the nuclear matrix. Microarray analysis showed that mutation of these lysine residues compromise Pax5 mediated activation and repression of hundreds target genes. Furthermore, chromatin immunoprecipitation (ChIP) and nuclear matrix foot printing assays indicated that Pax5 is responsible for recruitment of Cd19 loci to the nuclear matrix bound RNA polymerase complex. These results demonstrate that association with the nuclear matrix is essential for Pax5 to control the B lineage specific gene expression program.
- Copyright © 2011 by The American Association of Immunologists, Inc.