Regulation of Human FcεRI α-Chain Gene Expression by Multiple Transcription Factors

Abstract

Transcriptional regulation of the gene-encoding human FcεRI α-chain was analyzed in detail. EMSA revealed that either YY1 or PU.1 bound to the region close to that recognized by Elf-1. The α-chain promoter activity was up-regulated ∼2-fold by exogenously expressed YY1 or PU.1 and ∼7-fold by GATA-1, respectively, in KU812 cells. In contrast, coexpression of GATA-1 with either of PU.1 or YY1 dramatically activated the promoter ∼41- or ∼27-fold, respectively. Especially synergic activation by GATA-1 and PU.1 was surprising, because these transcription factors are known to inhibit the respective transactivating activities of each other. These up-regulating effects of PU.1 and YY1 with GATA-1 were inhibited by overexpression of Elf-1, indicating that Elf-1 serves as a repressor for the α-chain gene expression. Transcriptional regulation of the α-chain gene through four transcriptional factors is discussed.

Critical Roles for PU.1, GATA1, and GATA2 in the Expression of Human FcεRI on Mast Cells: PU.1 and GATA1 Transactivate FCER1A, and GATA2 Transactivates FCER1A and MS4A2

“…5A). This result indicates that knock- Binding motifs for GATA family and PU.1 in the FCER1A promoter were identified in our previous study (4,5). T allele at the 266 single nucleotide polymorphism site (shown with an asterisk) in the FCER1A gene causes an additional GATA motif resulting in the tandem repeat of GATA motifs (33,34).…”

“…In contrast, PU.1 and GATA1/GATA2 exhibit a cooperative function in mast cells, as follows: 1) PU.1 and GATA2 cooperatively induce mast cell development (20); 2) PU.1 and GATA1 synergistically transactivate cell type-specific gene regulation in mast cells (5,29); and 3) PU.1 is required for GATA1 expression in mast cells (30). In our previous studies, PU.1, GATA1, and GATA2 were identified as specific transcription factors that participate in the transcriptional regulation of certain genes expressed in mast cells, including human FCER1A (FcεRIa), mouse Ms4a2 (FcεRIb), mouse c-kit, and human ST2/ IL1RL1 (4,5,7,14,18,19). However, it has also been reported that knockdown of GATA1 and GATA2 by siRNA does not affect FcεRI expression in rodent mast cells and/or a basophilic cell line (10,11).…”

“…In our previous studies regarding the transcriptional regulation of FcεRI subunit genes, several transcription factors have been identified (4)(5)(6)(7)(8)(9). Among them, hematopoietic cell-specific transcription factors are known to be involved in mast cell/basophilspecific gene regulation.…”

“…Among them, hematopoietic cell-specific transcription factors are known to be involved in mast cell/basophilspecific gene regulation. Briefly, cooperation between PU.1 and GATA1 in FcεRI-positive cells (5), and the suppressive effect of FOG-1 on GATA1 in FcεRI-negative cells (7), determines the cell type-specific expression of human a and mouse b genes, respectively. In these previous studies, reporter assays and EMSAs were mainly used to identify and to analyze the role of the transcription factors regulating the promoter activation.…”

Polymorphisms in the FcεRIβ Promoter Region Affecting Transcription Activity: A Possible Promoter-Dependent Mechanism for Association between FcεRIβ and Atopy

“…Cells were transfected with 5 g of reporter plasmid to compare the effect of each SNP, or they were infected with 3 g of reporter plasmid and 3 g of expression plasmid for coexpression analysis. Transfection was performed by electroporation using a Bio-Rad Gene Pulsar II (Bio-Rad, Hercules, CA) as described previously (17). The luminescence of each cell lysate was measured using MicroLumat Plus (Berthold, Postfach, Germany) as described previously (14).…”