Genome-wide investigation of in vivo EGR-1 binding sites in monocytic differentiation

Genome Biol. 2009;10(4):R41. doi: 10.1186/gb-2009-10-4-r41. Epub 2009 Apr 19.


Background: Immediate early genes are considered to play important roles in dynamic gene regulatory networks following exposure to appropriate stimuli. One of the immediate early genes, early growth response gene 1 (EGR-1), has been implicated in differentiation of human monoblastoma cells along the monocytic commitment following treatment with phorbol ester. EGR-1 has been thought to work as a modifier of monopoiesis, but the precise function of EGR-1 in monocytic differentiation has not been fully elucidated.

Results: We performed the first genome-wide analysis of EGR-1 binding sites by chromatin immunoprecipitation with promoter array (ChIP-chip) and identified EGR-1 target sites in differentiating THP-1 cells. By combining the results with previously reported FANTOM4 data, we found that EGR-1 binding sites highly co-localized with CpG islands, acetylated histone H3 lysine 9 binding sites, and CAGE tag clusters. Gene Ontology (GO) analysis revealed enriched terms, including binding of molecules, in EGR-1 target genes. In addition, comparison with gene expression profiling data showed that EGR-1 binding influenced gene expression. Moreover, observation of in vivo occupancy changes of DNA binding proteins following PMA stimulation indicated that SP1 binding occupancies were dramatically changed near EGR-1 binding sites.

Conclusions: We conclude that EGR-1 mainly recognizes GC-rich consensus sequences in promoters of active genes. GO analysis and gene expression profiling data confirm that EGR-1 is involved in initiation of information transmission in cell events. The observations of in vivo occupancy changes of EGR-1 and SP1 suggest that several types of interplay between EGR-1 and other proteins result in multiple responses to EGR-1 downstream genes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylation
  • Binding Sites / genetics
  • Blotting, Western
  • Cell Differentiation / genetics*
  • Cell Line
  • Chromatin Immunoprecipitation
  • CpG Islands / genetics
  • Early Growth Response Protein 1 / genetics*
  • Early Growth Response Protein 1 / metabolism*
  • Gene Expression Profiling
  • Gene Expression Regulation / drug effects
  • Genome, Human / genetics*
  • Histones / metabolism
  • Humans
  • Lysine / metabolism
  • Monocytes / cytology
  • Monocytes / metabolism*
  • Oligonucleotide Array Sequence Analysis
  • RNA, Small Interfering / genetics
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sp1 Transcription Factor / metabolism
  • Tetradecanoylphorbol Acetate / pharmacology
  • Transfection


  • EGR1 protein, human
  • Early Growth Response Protein 1
  • Histones
  • RNA, Small Interfering
  • Sp1 Transcription Factor
  • Lysine
  • Tetradecanoylphorbol Acetate