Cell：表观遗传学重大突破，上千万美元，40多篇论文的成果

国际人类表观基因组协会（International Human Epigenome Consortium, IHEC）公布了一系列研究成果，包括表观遗传对免疫力、细胞系确定和细胞分化的影响。 

2011年，欧盟委员会启动了有史以来规模最大的投资项目，投资3000万欧元（约合4100万美元）进行人类表观基因组学的研究，他们希望能通过这个叫做“蓝图”（BLUEPRINT）的项目找出所有影响基因表达的DNA修饰位点，了解表观基因影响健康及疾病的机理。

11月17日，国际人类表观基因组协会IHEC在Cell等期刊中公布了41篇论文，报道了BLUEPRINT项目的多项成果，这为全面分析表观遗传迈进了一大步。

其中一项是分析了表观遗传学在免疫中的作用。研究人员利用来自英国的将近200个献血者的主要免疫细胞类型，解析了这些细胞的基因组和表观基因组组成，从中发现遗传学能解释其中大部分表观遗传突变。

加拿大麦吉尔大学的学者Tomi Pastinen表示，将表观遗传改变与遗传突变放在一起，就像是一个巨大的拼图，这能为研发新型治疗药剂提供新的靶点。

其它研究还包括分析血液和骨髓样品中的T细胞表观基因组，研究人员发现基因组某些部位中出现了DNA甲基化逐步缺失，还有血液中记忆T细胞具有与骨髓不同的表观遗传谱。

研究人员还分析了CD8+ T细胞，结果发现婴儿具有类似于先天免疫细胞的表观遗传和基因表达谱，这也部分解释了婴儿为何会更加容易感染传染病原体。

这些仅仅只是一部分IHEC研究人员的成果。“来自全球各地的科学家组成的这个创新性团队，他们发表的论文数量和多个主题探讨不仅反应了这一协会的重要性，而且也证明了多个学科专家的合作所带来的巨大力量，其潜在影响力远远超过单个项目，”加拿大CIHR，IHEC执行委员会主席Eric Marcotte表示。

原始出处：

Noncoding DNA variants in disease

The Allelic Landscape of Human Blood Cell Trait Variation and Links to Common Complex Disease

William J. Astle, Heather Elding, Tao Jiang, Dave Allen, Dace Ruklisa, Alice L. Mann, and others

Cell, Vol. 167, Issue 5

Genetic Drivers of Epigenetic and Transcriptional Variation in Human Immune Cells

Lu Chen, Bing Ge, Francesco Paolo Casale, Louella Vasquez, Tony Kwan, Diego Garrido-Martín, and others

Cell, Vol. 167, Issue 5

Lineage-Specific Genome Architecture Links Enhancers and Non-coding Disease Variants to Target Gene Promoters

Biola M. Javierre, Oliver S. Burren, Steven P. Wilder, Roman Kreuzhuber, Steven M. Hill, Sven Sewitz, and others

Cell, Vol. 167, Issue 5

Histone Acetylome-wide Association Study of Autism Spectrum Disorder

Wenjie Sun, Jeremie Poschmann, Ricardo Cruz-Herrera del Rosario, Neelroop N. Parikshak, Hajira Shreen Hajan, Vibhor Kumar, and others

Cell, Vol. 167, Issue 5

A Compendium of Chromatin Contact Maps Reveals Spatially Active Regions in the Human Genome

Anthony D. Schmitt, Ming Hu, Inkyung Jung, Zheng Xu, Yunjiang Qiu, Catherine L. Tan, and others

Cell Reports, Vol. 17, Issue 8

Pathways involved in cell fate determination and disease

β-Glucan Reverses the Epigenetic State of LPS-Induced Immunological Tolerance

Boris Novakovic, Ehsan Habibi, Shuang-Yin Wang, Rob J.W. Arts, Robab Davar, Wout Megchelenbrink, and others

Cell, Vol. 167, Issue 5

Glutaminolysis and Fumarate Accumulation Integrate Immunometabolic and Epigenetic Programs in Trained Immunity 

Rob J.W. Arts, Boris Novakovic, Rob ter Horst, Agostinho Carvalho, Siroon Bekkering, Ekta Lachmandas, and others

Cell Metabolism

Genome-Wide Profiles of Extra-cranial Malignant Rhabdoid Tumors Reveal Heterogeneity and Dysregulated Developmental Pathways

Hye-Jung E. Chun, Emilia L. Lim, Alireza Heravi-Moussavi, Saeed Saberi, Karen L. Mungall, Mikhail Bilenky, and others 

Cancer Cell, Vol. 29, Issue 3

Transcriptional Landscape of Human Tissue Lymphocytes Unveils Uniqueness of Tumor-Infiltrating T Regulatory Cells

Marco De Simone, Alberto Arrigoni, Grazisa Rossetti, Paola Gruarin, Valeria Ranzani, Claudia Politano, and others

Immunity, Vol. 45, Issue 5

Epigenomic Profiling of Human CD4+ T Cells Supports a Linear Differentiation Model and Highlights Molecular Regulators of Memory Development

Pawel Durek, Karl Nordström, Gilles Gasparoni, Abdulrahman Salhab, Christopher Kressler, Melanie de Almeida, and others

Immunity, Vol. 45, Issue 5 

CD8+ T Cells from Human Neonates Are Biased toward an Innate Immune Response

Ariel O. Galindo-Albarrán, Oscar H. López-Portales, Darely Y. Gutiérrez-Reyna, Otoniel Rodríguez-Jorge, José Antonio Sánchez-Villanueva, Oscar Ramírez-Pliego, and others

Cell Reports, Vol. 17, Issue 8 

The Hematopoietic Transcription Factors RUNX1 and ERG Prevent AML1-ETO Oncogene Overexpression and Onset of the Apoptosis Program in t(8;21) AMLs

Amit Mandoli, Abhishek A. Singh, Koen H.M. Prange, Esther Tijchon, Marjolein Oerlemans, Rene Dirks, and others 

Cell Reports, Vol. 17, Issue 8

Analysis of Normal Human Mammary Epigenomes Reveals Cell-Specific Active Enhancer States and Associated Transcription Factor Networks

Davide Pellacani, Misha Bilenky, Nagarajan Kannan, Alireza Heravi-Moussavi, David J.H.F. Knapp, Sitanshu Gakkhar, and others 

Cell Reports, Vol. 17, Issue 8

Distinct Trends of DNA Methylation Patterning in the Innate and Adaptive Immune Systems 

Ronald P. Schuyler, Angelika Merkel, Emanuele Raineri, Lucia Altucci, Edo Vellenga, Joost H.A. Martens, and others 

Cell Reports, Vol. 17, Issue 8

eFORGE: A Tool for Identifying Cell Type-Specific Signal in Epigenomic Data 

Charles E. Breeze, Dirk S. Paul, Jenny van Dongen, Lee M. Butcher, John C. Ambrose, James E. Barrett, and others

Cell Reports, Vol. 17, Issue 8 

The International Human Epigenome Consortium Data Portal

David Bujold, David Anderson de Lima Morais, Carol Gauthier, Catherine Côté, Maxime Caron, Tony Kwan, and others 

Cell Systems 

The BLUEPRINT Data Analysis Portal 

José María Fernández, Victor de la Torre, David Richardson, Romina Royo, Montserrat Puiggròs, Valentí Moncunill, and others 

Cell Systems

Epigenomic Co-localization and Co-evolution Reveal a Key Role for 5hmC as a Communication Hub in the Chromatin Network of ESCs

David Juan, Juliane Perner, Enrique Carrillo de Santa Pau, Simone Marsili, David Ochoa, Ho-Ryun Chung, and others

Cell Reports, Vol. 14, Issue 5 

Soft X-Ray Tomography Reveals Gradual Chromatin Compaction and Reorganization during Neurogenesis In Vivo 

Mark A. Le Gros, E. Josephine Clowney, Angeliki Magklara, Angela Yen, Eirene Markenscoff-Papadimitriou, Bradley Colquitt, and others

Cell Reports, Vol. 17, Issue 8

Identifying heterogeneity in epigenomic measurements

DNA Methylation Dynamics of Human Hematopoietic Stem Cell Differentiation

Matthias Farlik, Florian Halbritter, Fabian Müller, Fizzah A. Choudry, Peter Ebert, Johanna Klughammer, and others

Cell Stem Cell

Nucleosome Density ChIP-Seq Identifies Distinct Chromatin Modification Signatures Associated with MNase Accessibility

Alireza Lorzadeh, Misha Bilenky, Colin Hammond, David J.H.F. Knapp, Luolan Li, Paul H. Miller, and others

Cell Reports, Vol. 17, Issue 8

Epigenomic Deconvolution of Breast Tumors Reveals Metabolic Coupling between Constituent Cell Types

Vitor Onuchic, Ryan J. Hartmaier, David N. Boone, Michael L. Samuels, Ronak Y. Patel, Wendy M. White, and others

Cell Reports, Vol. 17, Issue 8

Decoding the DNA Methylome of Mantle Cell Lymphoma in the Light of the Entire B Cell Lineage

Ana C. Queirós, Renée Beekman, Roser Vilarrasa-Blasi, Martí Duran-Ferrer, Guillem Clot, Angelika Merkel, and others

Cancer Cell, Vol. 30, Issue 5

SnapShot: Epigenomic Assays

Martin Krzywinski, Martin Hirst

Cell, Vol. 167, Issue 5

Cell Press Special Editions are editorially curated article collections, grouped thematically into journal issue format.

Access and download International Human Epigenome Consortium research published in Cell Press journals conveniently packaged into two volumes, available now in digital edition. These digital editions are made freely available thanks to the generosity of our sponsors.

IHEC Digital Edition 1 

International Human Epigenome Consortium Digital Edition Volume 2

Papers from Other Journals

DeepBlue epigenomic data server: programmatic data retrieval and analysis of epigenome region sets

Albrecht, F., List, M., Bock, C. and Lengauer, T.

Nucleic Acids Res.

Quantitative comparison of DNA methylation assays for biomarker development and clinical applications

Bock, C., Halbritter, F., Carmona, F.J., Tierling, S., Datlinger, P., Assenov, Y., Berdasco, M., Bergmann, A.K., Booher, K., Busato, F., et al.; BLUEPRINT consortium

Nat. Biotechnol.

Identification and characterization of PKF118-310 as a KDM4A inhibitor

Franci, G., Sarno, F., Nebbioso, A., and Altucci, L.

Epigenetics

Allele-specific methylome and transcriptome analysis reveals widespread imprinting in the human placenta

Hamada, H., Okae, H., Toh, H., Chiba, H., Hiura, H., Shirane, K., Sato, T., Suyama, M., Yaegashi, N., Sasaki, H., and Arima, T.

Am. J. Hum. Genet.

Optimizing ChIP-seq peak detectors using visual labels and supervised machine learning

Hocking, T.D., Goerner-Potvin, P., Morin, A., Shao, X., Pastinen, T., and Bourque, G.

Bioinformatics

Early-life nutrition modulates the epigenetic state of specific rDNA genetic variants in mice

Holland, M.L., Lowe, R., Caton, P.W., Gemma, C., Carbajosa, G., Danson, A.F., Carpenter, A.A., Loche, E., Ozanne, S.E., and Rakyan, V.K.

Science 

reChIP-seq reveals widespread bivalency of H3K4me3 and H3K27me3 in CD4(+) memory T cells

Kinkley, S., Helmuth, J., Polansky, J.K., Dunkel, I., Gasparoni, G., Fröhler, S., Chen, W., Walter, J., Hamann, A., and Chung, H.R.

Nat. Commun.

Information recovery from low coverage whole-genome bisulfite sequencing

Libertini, E., Heath, S.C., Hamoudi, R.A., Gut, M., Ziller, M.J., Czyz, A., Ruotti, V., Stunnenberg, H.G., Frontini, M., Ouwehand, W.H., et al.

Nat. Commun.

Saturation analysis for whole-genome bisulfite sequencing data

Libertini, E., Heath, S.C., Hamoudi, R.A., Gut, M., Ziller, M.J., Herrero, J., Czyz, A., Ruotti, V., Stunnenberg, H.G., Frontini, M., et al.

Nat. Biotechnol.

c-Myc modulation & acetylation is a key HDAC inhibitor target in cancer

Nebbioso, A., Carafa, V., Conte, M., Tambaro, F.P., Abbondanza, C., Martens, J.H., Nees, M., Benedetti, R., Pallavicini, I., Minucci, S., et al.

Clin. Cancer Res.

Integrating epigenomic data and 3D genomic structure with a new measure of chromatin assortativity

Pancaldi, V., Carrillo-de-Santa-Pau, E., Javierre, B.M., Juan, D., Fraser, P., Spivakov, M., Valencia, A., and Rico, D.

Genome Biol 

Increased DNA methylation variability in type 1 diabetes across three immune effector cell types 

Paul, D.S., Teschendorff, A. E., Dang, M. A. N., Lowe, R., Hawa, M. I., Ecker, S., Cunningham, S., Fouts, A. R., Ramelius, A., Burden, F., et al.

Nat Commun., in press

Chromatin accessibility maps of chronic lymphocytic leukaemia identify subtypespecific epigenome signatures and transcription regulatory networks

Rendeiro, A.F., Schmidl, C., Strefford, J.C., Walewska, R., Davis, Z., Farlik, M., Oscier, D., and Bock, C.

Nat. Commun.

Combining transcription factor binding affinities with open-chromatin data for accurate gene expression prediction

Schmidt, F., Gasparoni, N., Gasparoni, G., Gianmoena, K., Cadenas, C., K. Polansky, J.K., Ebert, P., Nordstroem, K., Barann, M., Sinha, A., et al.

Nucleic Acids Res., in press

From profiles to function in epigenomics

Stricker, S.H., Köferle, A., and Beck, S

Nat. Rev. Genet., in press

Epigenetic dynamics of monocyte-to-macrophage differentiation

Wallner, S., Schröder, C., Leitao, E., Berulava, T., Haak, C., Beißer, D., Rahmann, S., Richter, A.S., Manke, T., Bonisch, U., et al.

Epigenetics Chromatin

Co-ChIP enables genome-wide mapping of histone mark co-occurrence at single-molecule resolution 

Weiner, A., Lara-Astiaso, D., Krupalnik, V., Gafni, O., David, E., Winter, D.R., Hanna, J.H., and Amit, I.

Nat. Biotechnol.