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

Soren Impey, Sean R. McCorkle, Hyunjoo Cha-Molstad, Jami M. Dwyer, Gregory S. Yochum, Jeremy M. Boss, Shannon McWeeney, John J. Dunn, Gail Mandel, Richard Goodman

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573 Scopus citations

Abstract

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 ∼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.

Original languageEnglish (US)
Pages (from-to)1041-1054
Number of pages14
JournalCell
Volume119
Issue number7
DOIs
Publication statusPublished - Dec 29 2004

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ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

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