title: Sensitive ChIP-DSL technology reveals an extensive estrogen receptor alpha-binding program on human gene promoters.
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.
authors.affiliation: Department of Cellular and Molecular Medicine, University of California at San Diego School of Medicine, La Jolla, CA 92093-0651, USA.
authors.forename: Young-Soo
authors.initials: YS
authors.lastname: Kwon
authors.forename: Ivan
authors.initials: I
authors.lastname: Garcia-Bassets
authors.forename: Kasey R
authors.initials: KR
authors.lastname: Hutt
authors.forename: Christine S
authors.initials: CS
authors.lastname: Cheng
authors.forename: Mingjie
authors.initials: M
authors.lastname: Jin
authors.forename: Dongyan
authors.initials: D
authors.lastname: Liu
authors.forename: Chris
authors.initials: C
authors.lastname: Benner
authors.forename: Dong
authors.initials: D
authors.lastname: Wang
authors.forename: Zhen
authors.initials: Z
authors.lastname: Ye
authors.forename: Marina
authors.initials: M
authors.lastname: Bibikova
authors.forename: Jian-Bing
authors.initials: JB
authors.lastname: Fan
authors.forename: Lingxun
authors.initials: L
authors.lastname: Duan
authors.forename: Christopher K
authors.initials: CK
authors.lastname: Glass
authors.forename: Michael G
authors.initials: MG
authors.lastname: Rosenfeld
authors.forename: Xiang-Dong
authors.initials: XD
authors.lastname: Fu
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics; D045744:Cell Line, Tumor; D047369:Chromatin Immunoprecipitation / Q000379:methods*; D004958:Estradiol / Q000494:pharmacology; D047628:Estrogen Receptor alpha / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D015894:Genome, Human / Q000187:drug effects / Q000235:genetics; D006657:Histones / Q000378:metabolism; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D011401:Promoter Regions, Genetic / Q000187:drug effects / Q000235:genetics*; D011485:Protein Binding / Q000187:drug effects
chemical_list: D047628:Estrogen Receptor alpha; D006657:Histones; D004958:Estradiol