Department of Pathology
Massachusetts General Hospital, Harvard Medical School and Broad Institute
Simches Research Building, CPZN 8234
185 Cambridge St.
Boston, MA 02114
Lab Members: 11 postdoctoral fellows, 4 graduate students, 2 technicians
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 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. Current projects in the lab are are focused on these 'bivalent' domains with the goals of understanding their initial establishment, their higher-order structure, and their roles in ES cell pluripotency and epigenetic regulation. 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 chromatin regulation during development, and how chromatin mis-regulation contributes to human disease.
Ram O, Goren A, Amit I, Shoresh N, Yosef N, Ernst J, Kellis M, Gymrek M, Issner R, Coyne M, Durham M, Zhang X, Donaghey J, Epstein CB, Regev A, Bernstein BE. Combinatorial patterning of chromatin regulators uncovered by genome-wide location analysis in human cells. Cell 2011; 147:1628-39.
Ernst J, Kheradpour P, Mikkelsen TS, Shoresh N, Ward LD, Epstein CB, Zhang X, Wang L, Issner R, Coyne M, Ku M, Durham T, Kellis M, Bernstein BE. Systematic analysis of chromatin state dynamics in nine human cell types. Nature 2011; 473:43-9.
Zhou VW, Goren A, Bernstein BE. Charting histone modifications and the functional organization of mammalian genomes. Nature Rev Genetics 2011; 12:7-18.
Mendenhall E, Koche RP, Zhou VW, Truong T, Issac J, Chi AS, Ku M, Bernstein BE. GC-rich sequence elements recruit PRC2 in mammalian ES cells. PloS Genet 2010; 6:e1001244. PMC3000368
Adli M, Zhu J, Bernstein BE. Genome-wide chromatin maps derived from limited numbers of hematopoietic progenitors. Nat Methods 2010; 7:599-600. PMC2924612
Presser-Aiden A, Rivera MN, Rheinbay E, Ku M, Coffman, E, Truong TT, Vargas SO, Lander ES, Haber DA, Bernstein BE. Chromatin analysis of Wilms tumor highlights stem cell properties and a renal developmental network. Cell Stem Cell 2010; 6:591-602. PMC2897075
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 Aug 2;448(7153):553-60.
For a complete listing of publications click here.
Last Update: 7/26/2012