Pip, a novel IRF family member, is a lymphoid-specific, PU.1-dependent transcriptional activator.

Abstract

The immunoglobulin light-chain gene enhancers EK3,, Ex2.4, and E~3. l contain a conserved cell type-specific composite element essential for their activities. This element binds a B cell-specific heterodimeric protein complex that consists of the Ets family member PU.1 and a second factor (NF-EMS), whose participation in the formation of the complex is dependent on the presence of DNA-bound PU.1. In this report we describe the cloning and characterization of Pip (_PU.I "_interaction partner), a lymphoid-specific protein that is most likely NF-EMS. As expected, the Pip protein binds the composite element only in the presence of PU.I; furthermore, the formation of this ternary complex is critically dependent on phosphorylation of PU.1 at serine-148. The P/p gene is expressed specifically in lymphoid tissues in both B-and T-cell lines. When coexpressed in NIH-3T3 cells, Pip and PU.1 function as mutually dependent transcription activators of the composite element. The amino-terminal DNA-binding domain of Pip exhibits a high degree of homology to the DNA-binding domains of members of the interferon regulatory factor (IRF) family, which includes IRF-1, IRF-2, ICSBP, and ISGF3~/.

Development of human plasmacytoid dendritic cells depends on the combined action of the basic helix‐loop‐helix factor E2‐2 and the Ets factor Spi‐B

“…The consensus E-box sequence (CANNTG) has been identified in a number of regulatory elements of lymphoid lineage specific genes, including the T-cell receptor a and b enhancers, the CD4 silencer and enhancer, and the promoters of mb-1, l5, and pTa, which are involved in either Bor T-cell development [26,[43][44][45][46][47][48]. Furthermore, it is possible that complexes consisting of Ets factors and IRF bind to ETS-IRF composite DNA elements (EICE) [49]. In addition, it has been reported that a ternary complex of PU.1, IRF-4, and E47, by binding to an E-box and EICE, transactivated expression of the CIITA gene, which was required for expression of MHC class II on B cells [50].…”

Co-occupancy of the interferon regulatory element of the class II transactivator (CIITA) Type IV promoter by interferon regulatory factors 1 and 2

“…This hetero-dimerization would be mediated by DNA binding, as IRFs exist as monomers in solution . In several other cases, synergistic activation of a promoter has been explained by the increase in promoter element binding induced by the physical interaction between two transcription factors (Pongubala et al, 1993;Eisenbeis et al, 1995;Neish et al, 1995;Sun et al, 1995;Pongubala and Atchison, 1997). For example, IRF-1 and NF-kB synergistically activate the endothelial VCAM-1 through physical interaction of IRF-1 with the p50 subunit of NF-kB (Neish et al, 1995).…”

“…The interferon regulatory factor (IRF) family is composed of several structurally related proteins including IRF-1 (Harada et al, 1989;Pine et al, 1990), IRF-2 (Harada et al, 1989), ICSBP (Nelson et al, 1993), ISGF3g (Veals et al, 1992), IRF-3 (Grant et al, 1995), IRF-7 (Zhang and Pagano, 1997), Pip (Eisenbeis et al, 1995), and LSIRF (Yamagata et al, 1996), which play a vital role in the regulation of interferon (IFN)-and virus-mediated responses. IRF-1 and IRF-2 are generally regarded as a pair of mutually antagonizing transcription factors.…”

Site-specific DNA methylation by a complex of PU.1 and Dnmt3a/b

“…PU.1 functions in concert with other transcription factors and cofactors, including c-Myb, C/EBPa (Oelgeschlager et al, 1996), NF-IL-6 (C/EBPd) (Nagulapalli et al, 1995), NF-EM-5/Pip (Eisenbeis et al, 1995), cFos (Bassuk and Leiden, 1995), c-Jun (Pongubala and Atchison, 1997), Rb (Konishi et al, 1999) and RUNX1/ AML1 (Zhang et al, 1994). We have previously reported that PU.1 interacts with CRE-binding protein (CBP) or p300, which functions as a coactivator for several transcription factors .…”