Overview of activities in the nucleus. Regulation of genome functions involved in complex interactions between DNA, histone and protein complexes within the nucleosomes to bring about highly controlled and organized nucleus activities, such as transcription, DNA repair and replication, critical for cellular development.

Future advances of ChIP-based approaches. (a) ChIA-PET represents a new approach to interrogate long-range inter- and intra-chromosomal interactions that are mediated by TFs or chromatin-modifying complexes to drive gene expression. (b) RNA immunoprecipitation method coupled with ultra-high-throughput sequencing (RIP-Seq).

Overview of ChIP-based analysis. (a) Schematic view of the ChIP method. (b) Outline of ChIP-chip method. Input DNA and ChIP DNA are fluorescently labeled and hybridized to an array of probes where intensities from individual probes are recorded. A high probe intensity from the ChIP DNA over the input DNA will represent a potential binding site. Here a red dot represents a potential protein-binding site. (c) ChIP-PET overview. ChIP DNA is cloned into a plasmid vector and converted into PETs via MmeI digestion. The released PETs are concatenated, cloned and sequenced. PET sequences are mapped back to the genome to locate the TF binding site. Sites with multiple overlapping PETs are regarded as potential TF binding sites, while singleton PETs are regarded as background and removed from the analysis. (d) ChIP-DSL scheme. The technique avoids direct amplification of ChIP DNA for hybridization, hence providing an unbiased amplification with increased sensitivity over ChIP-chip. (e) ChIP-SAGE. Summary of the ChIP-SAGE experimental procedure. (f) Illustration of ChIP-Seq. ChIP DNA is ligated with specific sequencing adaptors and PCR amplified. The PCR product is hybridized onto the surface of a flowcell for sequencing.