Genome-wide analysis of interferon regulatory factor I binding in primary human monocytes

Gene. 2011 Nov 1;487(1):21-8. doi: 10.1016/j.gene.2011.07.004. Epub 2011 Jul 19.

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Apoptosis Regulatory Proteins
  • Base Sequence
  • Binding Sites / genetics
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism
  • Cells, Cultured
  • Chromatin Immunoprecipitation / methods
  • Gene Expression / drug effects
  • Gene Expression Profiling*
  • Genome, Human / genetics*
  • Humans
  • Interferon Regulatory Factor-1 / genetics*
  • Interferon Regulatory Factor-1 / metabolism
  • Interferons / pharmacology
  • Interleukin-4 / pharmacology
  • Intracellular Signaling Peptides and Proteins / genetics
  • Intracellular Signaling Peptides and Proteins / metabolism
  • Monocytes / cytology
  • Monocytes / drug effects
  • Monocytes / metabolism*
  • Protein Binding
  • Proteins / genetics
  • Proteins / metabolism
  • RNA-Binding Proteins
  • Sequence Analysis, DNA / methods

Substances

  • Adaptor Proteins, Signal Transducing
  • Apoptosis Regulatory Proteins
  • Carrier Proteins
  • IFIT1 protein, human
  • IFIT2 protein, human
  • IFIT3 protein, human
  • IRF1 protein, human
  • Interferon Regulatory Factor-1
  • Intracellular Signaling Peptides and Proteins
  • Proteins
  • RNA-Binding Proteins
  • Interleukin-4
  • Interferons