E-WMIT-8 - Chromatin immunoprecipitation of human HNF3b and E2F4, and mouse NeuroD1, for THEME analysis
Submitted on 9 May 2006, released on 9 May 2006, last updated on 2 May 2014
Homo sapiens, Mus musculus
Genome-wide chromatin-immunoprecipitation (ChIP-chip) detects binding of transcriptional regulators to DNA in vivo at low resolution. Motif discovery algorithms can be used to discover sequence patterns in the bound regions that may be recognized by the immunoprecipitated protein. However, the discovered motifs often do not agree with the binding specificity of the protein, when it is known. RESULTS: We present a powerful approach to analyzing ChIP-chip data, called THEME, that tests hypotheses concerning the sequence specificity of a protein. Hypotheses are refined using constrained local optimization. Cross-validation provides a principled standard for selecting the optimal weighting of the hypothesis and the ChIP-chip data and for choosing the best refined hypothesis. We demonstrate how to derive hypotheses for proteins from 36 domain families. Using THEME together with these hypotheses, we analyze ChIP-chip datasets for 14 human and mouse proteins. In all the cases the identified motifs are consistent with the published data with regard to the binding specificity of the proteins.
ChIP-chip by array, binding site identification
A hypothesis-based approach for identifying the binding specificity of regulatory proteins from chromatin immunoprecipitation data. MacIsaac, Kenzie D.; Gordon, D. Benjamin; Nekludova, Lena; Odom, Duncan T.; Schreiber, Joerg; Gifford, David K.; Young, Richard A.; Fraenkel, Ernest. Bioinformatics 22(4):423 (2006), Europe PMC 16332710