| Transcriptional regulation is a crucial and widely studied aspect of gene expression. In September 2003, the National Human Genome Research Institute (NHGRI) launched a public research consortium named ENCODE, the ENCyclopedia Of DNA Elements, for development of experimental techniques and identification of functional regulatory elements in human genomic DNA. As a member of Dr. Weng's Lab which is one of the key data analysis hubs, I have been working on integration and mining of ENCODE datasets to study transcription factor binding. In addition, we have been collaborating directly with individual experimental labs within or outside of the ENCODE consortium to study transcriptional regulation in human and other eukaryotic genomes, using genomic annotations and algorithms developed for ENCODE.; Most of my analysis started from raw data produced by the TR (Transcriptional Regulation) subgroup of the ENCODE consortium, including processing of ChIP-chip and ChIP-sequencing datasets, cataloguing of regulatory factor binding regions and sequence motif discovery. By incorporating annotations from MSA (Multiple Sequence Alignment) and GT(Gene and Transcript) subgroups, cross-species comparison and anchored aggregation analysis elucidated novel characteristics for different transcription factors and markers. The most detailed case study was performed on a ChIP-sequencing p53 dataset, which showed extremely high sequence motif enrichment but lack of evolutionary constraint. We discovered sequence periodicity features flanking p53 binding sites which are associated to nucleosome positioning.; Nucleosome formation and DNA packaging have profound impact on chromatin structure and transcriptional regulation. We followed up by analyzing experimentally annotated stable nucleosome-forming genomic sequences, including those in Saccharomyces cerevisiae and Caenorhatmlais elegans genomes. Periodicities of different dinucleotides were quantified, and the association with nucleosome formation was supported by experimental evidence.; The tools and algorithms used in these studies have been applied to decipher regulatory functions of other transcription factors, such as human YY1, CTCF and mouse CREB Command-line toolkits and graphical web user interfaces were setup to provide streamlined access. |
