生物谷：雖然一個多細(xì)胞生物內(nèi)的各種不同細(xì)胞類型包含同一套基因,，但它們卻具有很不相同的行為。這些細(xì)胞狀態(tài)被認(rèn)為與染色質(zhì)狀態(tài)有關(guān),，也就是說,，與組蛋白和包裹基因組的其他蛋白的修飾有關(guān)。現(xiàn)在,，單分子測序技術(shù)被用來構(gòu)建小鼠胚胎干細(xì)胞和其他兩種在發(fā)育上更先進(jìn)的細(xì)胞類型的染色質(zhì)狀態(tài)圖,，從而顯示了重要染色質(zhì)修飾在整個基因組范圍內(nèi)的分布。該研究為將綜合染色質(zhì)甄別方法應(yīng)用于對各種不同的哺乳動物細(xì)胞群,、包括癌癥等疾病中所出現(xiàn)的異常細(xì)胞發(fā)育情況進(jìn)行定性研究提供了一個框架。
原始出處:
Nature 448, 553-560 (2 August 2007) | doi:10.1038/nature06008; Received 10 May 2007; Accepted 13 June 2007; Published online 1 July 2007
Genome-wide maps of chromatin state in pluripotent and lineage-committed cells
Tarjei S. Mikkelsen1,2, Manching Ku1,4, David B. Jaffe1, Biju Issac1,4, Erez Lieberman1,2, Georgia Giannoukos1, Pablo Alvarez1, William Brockman1, Tae-Kyung Kim5, Richard P. Koche1,2,4, William Lee1, Eric Mendenhall1,4, Aisling O'Donovan4, Aviva Presser1, Carsten Russ1, Xiaohui Xie1, Alexander Meissner3, Marius Wernig3, Rudolf Jaenisch3, Chad Nusbaum1, Eric S. Lander1,3,7 & Bradley E. Bernstein1,4,6,7
Broad Institute of Harvard and MIT,
Division of Health Sciences and Technology, MIT, and
Whitehead Institute for Biomedical Research, Cambridge, Massachusetts 02142, USA
Molecular Pathology Unit and Center for Cancer Research, Massachusetts General Hospital, Charlestown, Massachusetts 02129, USA
Department of Neurology, Children's Hospital, and
Department of Pathology, Harvard Medical School, Boston, Massachusetts 02115, USA
These authors contributed equally to this work.
Correspondence to: Eric S. Lander1,3,7Bradley E. Bernstein1,4,6,7 Correspondence and requests for materials should be addressed to E.S.L. (Email: [email protected]) or B.E.B. (Email: [email protected]).
Abstract
We report the application of single-molecule-based sequencing technology for high-throughput profiling of histone modifications in mammalian cells. By obtaining over four billion bases of sequence from chromatin immunoprecipitated DNA, we generated genome-wide chromatin-state maps of mouse embryonic stem cells, neural progenitor cells and embryonic fibroblasts. We find that lysine 4 and lysine 27 trimethylation effectively discriminates genes that are expressed, poised for expression, or stably repressed, and therefore reflect cell state and lineage potential. Lysine 36 trimethylation marks primary coding and non-coding transcripts, facilitating gene annotation. Trimethylation of lysine 9 and lysine 20 is detected at satellite, telomeric and active long-terminal repeats, and can spread into proximal unique sequences. Lysine 4 and lysine 9 trimethylation marks imprinting control regions. Finally, we show that chromatin state can be read in an allele-specific manner by using single nucleotide polymorphisms. This study provides a framework for the application of comprehensive chromatin profiling towards characterization of diverse mammalian cell populations.
