Chromatin profiling using targeted DNA adenine methyltransferase

Chromatin is the highly complex structure consisting of DNA and hundreds of associated proteins. Most chromatin proteins exert their regulatory and st ructural functions by binding to specific chromosomal loci. Knowledge of th e identity of these in vivo target loci is essential for the understanding of the functions and mechanisms of action of chromatin proteins. We report here large-scale mapping of in vivo binding sites of chromatin proteins, us ing a novel approach based on a combination of targeted DNA methylation and microarray technology. We show that three distinct chromatin proteins in D rosophila melanogaster cells each associate with specific sets of genes. HP 1 binds predominantly to pericentric genes and transposable elements. GAGA factor associates with euchromatic genes that are enriched in (GA), motifs, A Drosophila homolog of Saccharomyces cerevisiae Sir2p is associated with several active genes and is excluded from heterochromatin. High-resolution, genome-wide maps of target loci of chromatin proteins ('chromatin profiles ') provide new insights into chromatin structure and gene regulation.