Defining the CREB regulon: a genome-wide analysis of transcription factor regulatory regions

Cell. 2004 Dec 29;119(7):1041-54. doi: 10.1016/j.cell.2004.10.032.


The CREB transcription factor regulates differentiation, survival, and synaptic plasticity. The complement of CREB targets responsible for these responses has not been identified, however. We developed a novel approach to identify CREB targets, termed serial analysis of chromatin occupancy (SACO), by combining chromatin immunoprecipitation (ChIP) with a modification of SAGE. Using a SACO library derived from rat PC12 cells, we identified approximately 41,000 genomic signature tags (GSTs) that mapped to unique genomic loci. CREB binding was confirmed for all loci supported by multiple GSTs. Of the 6302 loci identified by multiple GSTs, 40% were within 2 kb of the transcriptional start of an annotated gene, 49% were within 1 kb of a CpG island, and 72% were within 1 kb of a putative cAMP-response element (CRE). A large fraction of the SACO loci delineated bidirectional promoters and novel antisense transcripts. This study represents the most comprehensive definition of transcription factor binding sites in a metazoan species.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Binding Sites
  • Chromatin Immunoprecipitation / methods
  • CpG Islands / genetics
  • Cyclic AMP / metabolism
  • Cyclic AMP Response Element-Binding Protein / genetics
  • Cyclic AMP Response Element-Binding Protein / metabolism*
  • DNA / genetics
  • DNA / metabolism
  • Gene Expression Regulation / drug effects
  • Gene Expression Regulation / radiation effects
  • Gene Library
  • Genome
  • Genomics*
  • Oligonucleotide Array Sequence Analysis
  • PC12 Cells
  • RNA, Antisense / genetics
  • RNA, Antisense / metabolism
  • Rats
  • Regulon / genetics*
  • Reproducibility of Results
  • Response Elements / genetics*
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Transcription, Genetic / genetics


  • Cyclic AMP Response Element-Binding Protein
  • RNA, Antisense
  • Transcription Factors
  • DNA
  • Cyclic AMP