Physical and Functional Interactions between Daxx and DNA Methyltransferase 1-Associated Protein, DMAP1

Abstract

Daxx has been shown to play an essential role in type I IFN-αβ-mediated suppression of B cell development and apoptosis. Recently, we demonstrated that Tyk2 is directly involved in IFN signaling for the induction and translocation of Daxx, which may result in growth arrest and/or apoptosis of B lymphocyte progenitors. To clarify how Daxx regulates B cell development, we examined Daxx interacting partners by yeast two-hybrid screening. DNA methyltransferase 1 (DNMT1)-associated protein (DMAP1) was identified and demonstrated to interact with Daxx. The interaction regions in both proteins were mapped, and the cellular localization of the interaction was examined. Both Daxx and DMAP1 formed a complex with DNMT1 and colocalized in the nucleus. DMAP1 enhanced Daxx-mediated repression of glucocorticoid receptor transcriptional activity. Furthermore, Daxx protected protein degradation of DMAP1 in vivo. These results provide the novel molecular link between Daxx and DNMT1, which establishes a repressive transcription complex in the nucleus.

Regulation of c-met expression by transcription repressor Daxx

“…Daxx was purified as a component of a multiprotein repression complex that includes HDAC1 and HDAC2, Dek and the core histones (Hollenbach et al, 1999(Hollenbach et al, , 2002Li et al, 2000a); it also interacts with DNMT1 and DMAP1 (Michaelson et al, 1999;Muromoto et al, 2004). In addition, Daxx forms a complex with protein ATRX and this complex displays chromatin-remodeling activity (Xue et al, 2003;Ishov et al, 2004;Tang et al, 2004).…”

Epstein–Barr virus-derived EBNA2 regulates STAT3 activation

“…Luciferase assay was performed as described [19]. Human Burkitt's lymphoma DG75 B cells were grown in RPMI 1640 medium containing 10% FBS.…”

Regulation of STAT3-mediated signaling by LMW-DSP2

“…(b) 293T cells in a 12-well plate were transfected with STAT3-LUC (0.4 mg) and/or indicated amounts of WT, D/A or C/S of LMW-DSP2 as described the above. (c and d) Human hepatoma cell line Hep3B and human cervix carcinoma cell line, HeLa, were maintained in DMEM containing 10% FCS (Imoto et al, 2003;Muromoto et al, 2004). Hep3B (c) and HeLa (d) cells in a 12-well plate were transfected with STAT3-LUC (0.5 mg) and/or indicated amounts of WT or D/A of LMW-DSP2 using jetPEI (PolyPlus-transfection).…”