Chromatin Modifications Distinguish Genomic Features and Physical Organization of the Nucleus

This chapter discusses the fact that chromatin modifications distinguish genomic features and physical organization of the nucleus. The spatial organization of genomic DNA in the nucleus thus represents the next frontier in functional genomics and epigenomics. The specific DNA sequences associated with a particular protein complex are then isolated by immuno-affinity purification using a specific antibody against the protein. The purified DNA fragments are assayed by a variety of molecular techniques, such as Southern blot or polymerase chain reaction (PCR), to determine association of particular DNA sequences with the protein of interest. This genome-wide approach to investigating protein-DNA interactions was extended by the adaptation of the Serial Analysis of Gene Expression (SAGE) technique to analysis of ChIP DNA. The extension of 3C analysis to the entire human genome, coupled with advances in imaging and FISH techniques, promises to provide us with a global understanding of how the entire genome is packaged into the nucleus and how the resulting three-dimensional topology of the genome influences its activity. Combined with detailed genome-wide maps of heterochromatin and euchromatin, an unprecedented molecular view of gene activity, epigenetic structure, and 3D organization of the genome will be possible.