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Variation in Transcription Factor Binding Among Humans

2010; American Association for the Advancement of Science; Volume: 328; Issue: 5975 Linguagem: Inglês

10.1126/science.1183621

1095-9203

Maya Kasowski, Fabian Grubert, Christopher Heffelfinger, Manoj Hariharan, Akwasi Asabere, Sebastian M. Waszak, Lukas Habegger, Joel Rozowsky, Minyi Shi, Alexander E. Urban, Mi-Young Hong, Konrad J. Karczewski, Wolfgang Huber, Sherman M. Weissman, Mark Gerstein, Jan O. Korbel, M Snyder,

Gene expression and cancer classification

Differences in gene expression may play a major role in speciation and phenotypic diversity. We examined genome-wide differences in transcription factor (TF) binding in several humans and a single chimpanzee by using chromatin immunoprecipitation followed by sequencing. The binding sites of RNA polymerase II (PolII) and a key regulator of immune responses, nuclear factor kappaB (p65), were mapped in 10 lymphoblastoid cell lines, and 25 and 7.5% of the respective binding regions were found to differ between individuals. Binding differences were frequently associated with single-nucleotide polymorphisms and genomic structural variants, and these differences were often correlated with differences in gene expression, suggesting functional consequences of binding variation. Furthermore, comparing PolII binding between humans and chimpanzee suggests extensive divergence in TF binding. Our results indicate that many differences in individuals and species occur at the level of TF binding, and they provide insight into the genetic events responsible for these differences.