Video: Demonstration of KAP1 Binding to Silenced Chromatin with Genome-wide ChIP-chip Analysis

Summary: Methylation of lysine residues on histone H3 and H4 tails plays a key role in gene regulation, chromatin structure, and establishment and maintenance of epigenetic memory. In particular, methylation of lysines 9 or 27 of histone H3 (H3me3K9 and H3me3K27, respectively) have been associated with silenced chromatin. ChIP-chip analysis using human promoter arrays indicate that the two marks segregate differentially with the two most common types of transcription factors; H3me3K9 is highly enriched at zinc finger genes (ZNFs) and H3me3K27 is highly enriched at homeobox genes. Here we show that many promoters containing the H3me3K9 mark are also bound by the corepressor KAP1 (also known as TIF1B or TRIM28). We then performed a complete genomic analysis using a set of 38 tiling arrays, which identified ~7000 KAP1 binding sites in the entire human genome. KAP1 binding was specifically enriched at zinc finger genes. Although most KAP1 binding sites were within core promoter regions, a unique binding pattern was observed at ZNF target genes. Analysis of ChIP-chip data from promoter arrays as well as from whole genome tiling arrays will be discussed.