Global changes in specific histone modifications in cancer

Division Of Basic Sciences - Nci

Investigators

Abstract

We have made substantial improvements to the processing of samples for RPA and improved the detection by using fluorescence and chemiluminescence methods in place of immunohistochemistry. We have also identified the sources of variability in the preparation of microarrays and devised protocols that minimize or correct for sample-to-sample variation. We have validated antibodies to over 30 different PTMs on histones including various residue specific or general acetylations, methylations and phosphorylations. Applying this panel of antibodies across a spectrum of pathological and physiological samples including both tissues and cell lines has revealed promising associations of particular patterns of global modification with particular entities. For example, using heat maps, samples sort according to their biological relatedness. This system can be expanded to explore the chromatin proteomics of a variety of tumors and to observed the response to therapy that is designed to exacerbate or inhibit chromatin modification inorder to manipulate the genetic and epigenetic programs in tumor cells.