Genome-Wide Chromosomal Targets of Oncogenic Transcription Factors; Final rept. 31 Mar 2004-30 Mar 2008

摘要

We proposed to develop a new genomic method named STAGE (Sequence Tag Analysis of Genomic Enrichment) to identify the direct downstream targets of transcription factors important in breast cancer. STAGE was based on high- throughput sequencing of concatamerized tags derived from DNA associated with transcription factors isolated by chromatin immunoprecipitation. We have successfully accomplished the original goals of the project. The advent of next- generation sequencing technologies (Solexa, 454) after the inception of this project provided new opportunities to enhance our original idea of developing sequencing based methods of target identification. We have taken advantage of the power of next generation sequencing, and applied it to several transcription factors important in cancer and cell proliferation. Since the binding and function of transcription factors is strongly governed by chromatin and positions of nucleosomes, we have also adapted the sequencing approach to identify positioned nucleosomes genome-wide at high resolution.