Sensitive ChIP-DSL technology reveals an extensive estrogen receptor alpha-binding program on human gene promoters.

TitleSensitive ChIP-DSL technology reveals an extensive estrogen receptor alpha-binding program on human gene promoters.
Publication TypeJournal Article
Year of Publication2007
AuthorsKwon Y-S, Garcia-Bassets I, Hutt KR, Cheng CS, Jin M, Liu D, Benner C, Wang D, Ye Z, Bibikova M, Fan J-B, Duan L, Glass CK, Rosenfeld MG, Fu X-D
JournalProc Natl Acad Sci U S A
Volume104
Issue12
Pagination4852-7
Date Published2007 Mar 20
ISSN0027-8424
KeywordsBreast Neoplasms, Cell Line, Tumor, Chromatin Immunoprecipitation, Estradiol, Estrogen Receptor alpha, Female, Gene Expression Regulation, Neoplastic, Genome, Human, Histones, Humans, Oligonucleotide Array Sequence Analysis, Promoter Regions, Genetic, Protein Binding
Abstract

ChIP coupled with microarray provides a powerful tool to determine in vivo binding profiling of transcription factors to deduce regulatory circuitries in mammalian cells. Aiming at improving the specificity and sensitivity of such analysis, we developed a new technology called ChIP-DSL using the DNA selection and ligation (DSL) strategy, permitting robust analysis with much reduced materials compared with standard procedures. We profiled general and sequence-specific DNA binding transcription factors using a full human genome promoter array based on the ChIP-DSL technology, revealing an unprecedented number of the estrogen receptor (ERalpha) target genes in MCF-7 cells. Coupled with gene expression profiling, we found that only a fraction of these direct ERalpha target genes were highly responsive to estrogen and that the expression of those ERalpha-bound, estrogen-inducible genes was associated with breast cancer progression in humans. This study demonstrates the power of the ChIP-DSL technology in revealing regulatory gene expression programs that have been previously invisible in the human genome.

DOI10.1073/pnas.0700715104
PubMed URLhttp://www.ncbi.nlm.nih.gov/pubmed/17360330?dopt=Abstract
PMCPMC1821125
Alternate JournalProc. Natl. Acad. Sci. U.S.A.
PubMed ID17360330