Bradley Bernstein

Department of Pathology
Massachusetts General Hospital and Harvard Medical School
Genome Biology and Cell Circuits Program, Broad Institute
149 13th St. Room 7148
Charlestown, MA 02129
Tel: 617-726-6906
Fax: 617-726-5684
Email: bbernstein@partners.org
2 postdoctoral fellows, 1 graduate student, 1 technician

Though much of what defines a human is encoded in the sequence of our DNA, many additional factors influence how this genetic information is manifest. For example, heritable epigenetic information contained within chromatin, the higher-order structure that packages the genome, has critical functions during embryonic development and can contribute to the pathogenesis of disease. Our laboratory applies array-based and high-throughput sequencing-based technologies to characterize chromatin structure genome-wide in human and mouse. In addition to advancing technology and providing unprecedented global views of mammalian chromatin, this work has led to an appreciation of the role of large-scale chromatin structures, or ‘domains’, in regulating developmental genes. In differentiated cells, chromatin domains marked by either ‘active’ or ‘repressive’ histone modifications maintain expression or repression of key developmental genes (‘master regulators’). However, in pluripotent ES cells, chromatin domains enriched for both active and repressive modifications repress developmental genes while maintaining their potential for subsequent activation. These ‘bivalent’ domains appear to represent an epigenetic signature of pluripotency. Current projects in the lab are aimed at understanding how bivalent domains are established in ES cells, and how they contribute to pluripotency. Similar approaches are also being used to characterize chromatin modifications in adult stem cells and cancer models. Our long-term goal is to achieve a systems level understanding of how chromatin domains are established, how they regulate gene expression during development, and how their mis-regulation contributes to human disease.

References:

• Mikkelsen TS, Ku M, Jaffe DB, Issac B, Lieberman E, Giannoukos G, Alvarez P, Brockman W, Kim TK, Koche RP, Lee W, Mendenhall E, O'Donovan A, Presser A, Russ C, Xie X, Meissner A, Wernig M, Jaenisch R, Nusbaum C, Lander ES, Bernstein BE. Genome-wide maps of chromatin state in pluripotent and lineage-committed cells. Nature 2007; 448:553-560.
• Bernstein BE, Meissner A, Lander ES. The mammalian epigenome. Cell 2007;128:669-81.
• Bernstein BE, Mikkelsen TS, Xie X, Kamal M, Huebert DJ, Cuff J, Fry B, Meissner A, Wernig M, Plath K, Jaenisch R, Wagschal A, Feil R, Schreiber SL, Lander ES. A bivalent chromatin structure marks key developmental genes in embryonic stem cells. Cell 2006;125:315-26.
• Bernstein BE, Kamal M, Lindblad-Toh K, Bekiranov S, Bailey DK, Huebert DJ, McMahon S, Karlsson EK, Kulbokas EJ, Gingeras TR, Schreiber SL, Lander ES. Genomic maps and comparative analysis of histone modifications in human and mouse. Cell 2005;120:169-81.
• Schreiber SL, Bernstein BE. Signaling network model of chromatin. Cell 2002;111:771-778.