title: Genome-wide analysis of interferon regulatory factor I binding in primary human monocytes.
abstract: IRF1 is a transcription factor that participates in interferon signaling. Previous studies of IRF1 binding have utilized in vitro assays. We used ChIP-seq in human monocytes to better define the recognition motif for IRF1. The newly identified 18bp motif (RAAASNGAAAGTGAAASY) is a refinement of the 13bp IRF1 motif commonly used. We utilized the 18bp consensus motif and identified 345 potential target genes. To compare the 18bp motif with the 13bp motif, we compared putative gene targets. Only 56 potential gene targets were defined by both consensus motifs. To compare biological effects of interferon on the 13bp and the 18bp consensus targets, we mined expression data from cells exposed to interferons or transfected with IRF1. In all cases, the 18bp consensus motif was more strongly associated with transcriptional responses than the 13bp motif. Therefore, the new 18bp consensus motif appears to have a greater association with biological activities of IRF1.
authors.affiliation: Department of Pediatrics, The Children's Hospital of Philadelphia, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
authors.forename: Lihua
authors.initials: L
authors.lastname: Shi
authors.forename: Juan C
authors.initials: JC
authors.lastname: Perin
authors.forename: Jeremy
authors.initials: J
authors.lastname: Leipzig
authors.forename: Zhe
authors.initials: Z
authors.lastname: Zhang
authors.forename: Kathleen E
authors.initials: KE
authors.lastname: Sullivan
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D051017:Apoptosis Regulatory Proteins; D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D047369:Chromatin Immunoprecipitation / Q000379:methods; D015870:Gene Expression / Q000187:drug effects; D020869:Gene Expression Profiling; D015894:Genome, Human / Q000235:genetics*; D006801:Humans; D050856:Interferon Regulatory Factor-1 / Q000235:genetics* / Q000378:metabolism; D007372:Interferons / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D009000:Monocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D011485:Protein Binding; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D016601:RNA-Binding Proteins; D017422:Sequence Analysis, DNA / Q000379:methods
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D051017:Apoptosis Regulatory Proteins; D002352:Carrier Proteins; C484290:IFIT1 protein, human; C484289:IFIT2 protein, human; C116468:IFIT3 protein, human; C494257:IRF1 protein, human; D050856:Interferon Regulatory Factor-1; D047908:Intracellular Signaling Peptides and Proteins; D011506:Proteins; D016601:RNA-Binding Proteins; D015847:Interleukin-4; D007372:Interferons