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ChIP-on-chip

Genome-Wide Screen of Transcription Factor Binding Sites
A review of Serum response factor binding sites differ in three human cell types.

Note: This is a review of the published article listed below. All information, quotes, figures, methods, and findings mentioned in this review are from that article, and are the property of its authors and/or the publication in which the article originally appeared.

The serum response factor (SRF) is a MADS-box transcription factor with divergent roles in embryonic development and maintenance of muscle cells and neurons, as well as being correlated to human diseases such as cancer and heart disease. To explore the relationship between SRF and the ability to bind to diverse cell types, Cooper et al. (2007) used Agilent’s ChIP and human promoter microarrays to perform genome-wide characterization of SFR binding sites in cell lines representing three different tissue types. The group identified more than 200 SRF binding sites, confirming binding at known sites, but also identifying many novel sites, while also seeking to identify the mechanism by which SRF binding sites were influenced. Based on results from the study, the authors suggest that SRF cofactors play an important role in determining cell-dependent SRF binding sites. This research provides a more complete understanding of elements that regulate genes in this network and ultimately predict their effects, individually and cumulatively, on gene expression. In characterizing regulatory events associated with SRF-related genes, new insights may be gleaned into diverse metabolic processes, including those associated with human development and disease.

Table 1. Quantitative PCR validation of array data
For each range of Z-scores listed, we tested enrichment of the unamplified array input. The data filter required more than one probe per region and data from more than one of three arrays. We report the number of tested regions with significant (>3) and moderate (>2) enrichment by quantitative PCR for each range of Z-scores. We observed decreasing validation rate with decreasing Z-score.


Figure 1. SRF binding in three cell types.
For each cell type and each putative target, the intensity of red indicates size of the Z-score obtained from the arrays. The right panel displays a subset of genes bound specifically by SRF in neurons (top) and smooth muscle cells (bottom). Gene names followed by an asterisk have been validated by quantitative PCR or were previously known.

Title: Serum response factor binding sites differ in three human cell types.
Authors: Cooper SJ, Trinklein ND, Nguyen L, Myers RM.
Journal: Genome Res. 2007 Feb;17(2):136-44.
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