RRC ID 47709
Author Yashiro T, Hara M, Ogawa H, Okumura K, Nishiyama C.
Title Critical Role of Transcription Factor PU.1 in the Function of the OX40L/TNFSF4 Promoter in Dendritic Cells.
Journal Sci Rep
Abstract PU.1 is a hematopoietic lineage-specific transcription factor belonging to the Ets family. We investigated the role of PU.1 in the expression of OX40L in dendritic cells (DCs), because the regulatory mechanism of cell type-specific expression of OX40L, which is mainly restricted to antigen-presenting cells, is largely unknown despite the critical involvement in Th2 and Tfh development. PU.1 knockdown decreased the expression of OX40L in mouse DCs. Chromatin immunoprecipitation (ChIP) assays demonstrated that PU.1 constitutively bound to the proximal region of the OX40L promoter. Reporter assays and electrophoretic mobility shift assays revealed that PU.1 transactivated the OX40L promoter through direct binding to the most-proximal Ets motif. We found that this Ets motif is conserved between mouse and human, and that PU.1 bound to the human OX40L promoter in ChIP assay using human monocyte-derived DCs. ChIP assays based on ChIP-seq datasets revealed that PU.1 binds to several sites distant from the transcription start site on the OX40L gene in addition to the most-proximal site in mouse DCs. In the present study, the structure of the OX40L promoter regulated by PU.1 is determined. It is also suggested that PU.1 is involved in mouse OX40L expression via multiple binding sites on the gene.
Volume 6
Pages 34825
Published 2016-10-6
DOI 10.1038/srep34825
PII srep34825
PMID 27708417
PMC PMC5052589
MeSH Animals Dendritic Cells / physiology* Female Gene Expression Regulation Gene Knockdown Techniques HEK293 Cells Humans Membrane Glycoproteins / genetics* Membrane Glycoproteins / metabolism Mice, Inbred BALB C Mice, Inbred C57BL Nucleotide Motifs OX40 Ligand / genetics OX40 Ligand / metabolism Promoter Regions, Genetic* Proto-Oncogene Proteins / genetics Proto-Oncogene Proteins / metabolism* Trans-Activators / genetics Trans-Activators / metabolism* Transcription Initiation Site Transcriptional Activation Tumor Necrosis Factors / genetics* Tumor Necrosis Factors / metabolism
IF 4.011
Times Cited 10
WOS Category IMMUNOLOGY
Resource
DNA material pGL4-OX40Lp-700b (RDB14536)