We propose to use our high-throughput production facility for genome-wide identification of the chromosomal locations of regulatory elements in human and mouse cells. Sequence-specific and general transcription factors will be mapped across the genome using chromatin immunoprecipitation followed by DNA sequencing (ChlP-Seq). Long noncoding RNAs (IncRNAs) will be mapped using ChlRP-seq, a method by which specific chromatin-bound RNAs and their associated regions are isolated using oligonucleotides followed by sequencing of the precipitated DNA. The results obtained from our genome wide mapping experiments will greatly advance the efforts of the ENCODE consortium to comprehensively identify all functional elements in the human genome. Our experimental data will be subjected to stringent quality metrics already established by the consortium and the results made publicly available in a timely manner. Targeted biological validation experiments will be performed, along with integrative analyses. All experiments and analyses will be performed by a highly experienced and well-integrated team of experts that has already established a successful working relationship. We expect our center to contribute greatly to the annotation of the human and mouse genomes.
A map of regulatory information is a valuable resource for understanding human biology and our genetic diversity. It is also valuable because a majority of single nucleotide polymorphisms that are associated with disease lie outside protein coding genes and are postulated to affect regulatory elements. Data from our project will be an important resource to help clinical scientists identify changes in regulatory regions that contribute to many human diseases.
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