Abstract
BackgroundSNP microarrays are designed to genotype Single Nucleotide Polymorphisms (SNPs). These microarrays report hybridization of DNA fragments and therefore can be used for the purpose of detecting genomic fragments.ResultsHere, we demonstrate that a SNP microarray can be effectively used in this way to perform chromatin immunoprecipitation (ChIP) on chip as an alternative to tiling microarrays. We illustrate this novel application by mapping whole genome histone H4 hyperacetylation in human myoblasts and myotubes. We detect clusters of hyperacetylated histone H4, often spanning across up to 300 kilobases of genomic sequence. Using complementary genome-wide analyses of gene expression by DNA microarray we demonstrate that these clusters of hyperacetylated histone H4 tend to be associated with expressed genes.ConclusionThe use of a SNP array for a ChIP-on-chip application (ChIP on SNP-chip) will be of great value to laboratories whose interest is the determination of general rules regarding the relationship of specific chromatin modifications to transcriptional status throughout the genome and to examine the asymmetric modification of chromatin at heterozygous loci.
Highlights
SNP microarrays are designed to genotype Single Nucleotide Polymorphisms (SNPs)
To illustrate the Chromatin immunoprecipitation (ChIP) on SNP-chip methodology, we present here a genome-wide analysis of histone H4 hyperacetylation in human myoblasts and myotubes
Complementary analysis of gene expression of the same samples indicates that histone H4 hyperacetylation is positively associated with gene expression at a range of [-300 Kb, +300 Kb] from the start of gene transcription; a much greater range than previously reported. These results show that ChIP on SNP-chip can be used to provide biological insight into how histone H4 hyperacetylation affects both eukaryotic transcription and chromatin's structural integrity
Summary
SNP microarrays are designed to genotype Single Nucleotide Polymorphisms (SNPs). These microarrays report hybridization of DNA fragments and can be used for the purpose of detecting genomic fragments. Several methodologies have been devised for the detection of the genomic fragments generated by a ChIP experiment (reviewed in [2]). The use of DNA microarray methodology (ChIP-on-chip) allows for high-throughput analysis of thousands of genomic sequences simultaneously [3]. Genome tiling arrays covering entire genomes [4] can be used to map the sites of DNA-protein interaction on a genomic scale, at a high cost. SNP microarrays are designed to genotype thousands of Single Nucleotide Polymorphisms (SNPs) by hybridization of genomic fragments to an array of short nucleotide sequences [5]. To illustrate the ChIP on SNP-chip methodology, we present here a genome-wide analysis of histone H4 hyperacetylation in human myoblasts and myotubes
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