To study allelic gene expression globally, we reengineered the assay and analysis of the Affymetrix SNP chip so that it measures allele-specific transcript variation. We observed gene expression differences between the two chromosomes within the same individual. The relative expression of specific alleles, however, varied between individuals suggesting a dependence on genomic context. We have observed differences due to haplotypes, chromatin features, and DNA methylation status. These studies from our lab have established that allelic variation in gene expression is common throughout the human genome. In addition, our studies indicate that genetics is an important factor that influences global chromatin state mediated by histone modification, the hallmark of the epigenetic phenomena. We are currently applying the SNP array technology to study global allele-specific DNA methylation. Furthermore, we are investigating the various mechanisms, including genetic polymorphism, epigenetic modifications, and post-transcriptional processing that can regulate differential allelic gene expression. We are also extending our research by characterize allele-specific gene expression and epigenetic modifications using breast cancer cell lines and breast primary tumors.
|Lee, Maxwell P (2012) Allele-specific gene expression and epigenetic modifications and their application to understanding inheritance and cancer. Biochim Biophys Acta 1819:739-42|
|Su, Hua; Hu, Nan; Yang, Howard H et al. (2011) Global gene expression profiling and validation in esophageal squamous cell carcinoma and its association with clinical phenotypes. Clin Cancer Res 17:2955-66|
|Kadota, Mitsutaka; Yang, Howard H; Gomez, Bianca et al. (2010) Delineating genetic alterations for tumor progression in the MCF10A series of breast cancer cell lines. PLoS One 5:e9201|
|Yang, Howard H; Hu, Nan; Wang, Chaoyu et al. (2010) Influence of genetic background and tissue types on global DNA methylation patterns. PLoS One 5:e9355|
|Kadota, Mitsutaka; Sato, Misako; Duncan, Beverly et al. (2009) Identification of novel gene amplifications in breast cancer and coexistence of gene amplification with an activating mutation of PIK3CA. Cancer Res 69:7357-65|