Bachelor of Science, University of British Columbia (2002)
Doctor of Philosophy, University of Washington (2010)
Jonathan Pritchard, Postdoctoral Faculty Sponsor
Histone modifications are important markers of function and chromatin state, yet the DNA sequence elements that direct them to specific genomic locations are poorly understood. Here, we identify hundreds of quantitative trait loci, genome-wide, that affect histone modification or RNA polymerase II (Pol II) occupancy in Yoruba lymphoblastoid cell lines (LCLs). In many cases, the same variant is associated with quantitative changes in multiple histone marks and Pol II, as well as in deoxyribonuclease I sensitivity and nucleosome positioning. Transcription factor binding site polymorphisms are correlated overall with differences in local histone modification, and we identify specific transcription factors whose binding leads to histone modification in LCLs. Furthermore, variants that affect chromatin at distal regulatory sites frequently also direct changes in chromatin and gene expression at associated promoters.
View details for DOI 10.1126/science.1242429
View details for Web of Science ID 000326647600046
View details for PubMedID 24136359