期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 104, 期 12, 页码 4852-4857出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0700715104
关键词
breast cancer; genome-wide; promoter array
资金
- NCI NIH HHS [CA114184, R33 CA114184] Funding Source: Medline
- NHGRI NIH HHS [R01 HG003119, HG003119] Funding Source: Medline
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 technoiogy, revealing an unprecedented number of the estrogen receptor (ER alpha) target genes in MCF-7 cells. Coupled with gene expression profiling, we found that only a fraction of these direct ER alpha target genes were highly responsive to estrogen and that the expression of those ER alpha-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.
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