Proteome analysis of chromatin complexes in differentiating stem cells

Abstract

Regulation of gene expression by proteins associated with chromatin is a major, yet poorly understood, feature of differentiation and development. Recent genomic studies have highlighted the role of chromatin regulatory proteins in pathologies affecting cellular proliferation and cell cycle, such as cancer. Mass spectrometry-based proteomics approaches have, in the last decade, provided a wealth of information on the dynamic nature of the proteome during cellular differentiation. Label-based approaches have predominated the literature, however, with the development of increasingly sensitive mass spectrometers and liquid chromatographic systems; label-free techniques offer a compelling alternative. Using these approaches, a vast repertoire of proteins have been identified in the proteome of undifferentiated and differentiating stem cells, including transcription factors, chromatin-modifying complexes, histone-modifying enzymes and signalling proteins which act in concert to regulate gene expression. Given the recent correlation between mutations in epigenetic machinery and the development and progression of various cancers, application of these approaches to the study cancer cell proteomes could provide valuable insights into the role of epigenetic reregulation in tumourogenesis.