Next-generation
sequencing of patient DNA could allow for personalized medicine, but needs
additional genomic annotation to be more useful. Application of new genomic
technologies for better understanding the functional elements of the genome in
a genome-wide manner can provide the necessary details. In this talk, I will
discuss the novel findings from the application of two genomic technologies.
First, Chromatin Interaction Analysis with Paired-End Tag sequencing
(ChIA-PET) is a next-generation sequencing-based method for identifying
chromatin interactions between transcription factor binding sites on a
genome-wide scale. Our results suggest that chromatin interactions may be a
major mechanism by which transcription regulation occurs in human cells.
Second, the combination of exonuclease digestion with Chromatin
Immunoprecipitation (ChIP-exo) is a method for obtaining precise transcription
factor binding site maps in the genome. Our results indicate that different
DNA-binding proteins have very different, unique binding properties to the DNA,
and may exclude a larger region than their known DNA motifs, suggesting steric
hindrance due to the structure of the factor or the involvement of cofactors.