2007 August 2 | Tarjei S. Mikkelsen, Manching Ku, David B. Jaffe, Biju Issac, Erez Lieberman, Georgia Giannoukos, Pablo Alvarez, William Brockman, Tae-Kyung Kim, Richard P. Koche, William Lee, Eric Mendenhall, Aisling O'Donovan, Aviva Presser, Carsten Russ, Xiaohui Xie, Alexander Meissner, Marius Wernig, Rudolf Jaenisch, Chad Nusbaum, Eric S. Lander, Bradley E. Bernstein
This study reports the application of single molecule-based sequencing technology to profile histone modifications in mammalian cells. By sequencing over 4 billion bases of chromatin immunoprecipitated DNA, the authors generated genome-wide chromatin state maps for mouse embryonic stem cells, neural progenitor cells, and embryonic fibroblasts. The maps reveal that lysine 4 and lysine 27 tri-methylation effectively discriminate genes that are expressed, poised for expression, or stably repressed, reflecting cell state and lineage potential. Lysine 36 tri-methylation marks primary coding and non-coding transcripts, facilitating gene annotation. Lysine 9 and lysine 20 tri-methylation are detected at satellite, telomeric, and active long-terminal repeats, and can spread into proximal unique sequences. Lysine 4 and lysine 9 tri-methylation mark imprinting control regions. The study also demonstrates that chromatin state can be read in an allele-specific manner using single nucleotide polymorphisms. This work provides a framework for comprehensive chromatin profiling to characterize diverse mammalian cell populations.This study reports the application of single molecule-based sequencing technology to profile histone modifications in mammalian cells. By sequencing over 4 billion bases of chromatin immunoprecipitated DNA, the authors generated genome-wide chromatin state maps for mouse embryonic stem cells, neural progenitor cells, and embryonic fibroblasts. The maps reveal that lysine 4 and lysine 27 tri-methylation effectively discriminate genes that are expressed, poised for expression, or stably repressed, reflecting cell state and lineage potential. Lysine 36 tri-methylation marks primary coding and non-coding transcripts, facilitating gene annotation. Lysine 9 and lysine 20 tri-methylation are detected at satellite, telomeric, and active long-terminal repeats, and can spread into proximal unique sequences. Lysine 4 and lysine 9 tri-methylation mark imprinting control regions. The study also demonstrates that chromatin state can be read in an allele-specific manner using single nucleotide polymorphisms. This work provides a framework for comprehensive chromatin profiling to characterize diverse mammalian cell populations.