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      The International Human Epigenome Consortium: A Blueprint for Scientific Collaboration and Discovery

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          Abstract

          The International Human Epigenome Consortium (IHEC) coordinates the generation of a catalog of high-resolution reference epigenomes of major primary human cell types. The studies now presented (see the Cell Press IHEC web portal at http://www.cell.com/consortium/IHEC) highlight the coordinated achievements of IHEC teams to gather and interpret comprehensive epigenomic datasets to gain insights in the epigenetic control of cell states relevant for human health and disease. PAPERCLIP.

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          Most cited references24

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

          Summary Innate immune memory is the phenomenon whereby innate immune cells such as monocytes or macrophages undergo functional reprogramming after exposure to microbial components such as lipopolysaccharide (LPS). We apply an integrated epigenomic approach to characterize the molecular events involved in LPS-induced tolerance in a time-dependent manner. Mechanistically, LPS-treated monocytes fail to accumulate active histone marks at promoter and enhancers of genes in the lipid metabolism and phagocytic pathways. Transcriptional inactivity in response to a second LPS exposure in tolerized macrophages is accompanied by failure to deposit active histone marks at promoters of tolerized genes. In contrast, β-glucan partially reverses the LPS-induced tolerance in vitro. Importantly, ex vivo β-glucan treatment of monocytes from volunteers with experimental endotoxemia re-instates their capacity for cytokine production. Tolerance is reversed at the level of distal element histone modification and transcriptional reactivation of otherwise unresponsive genes.
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            Quantitative comparison of DNA methylation assays for biomarker development and clinical applications.

            (2016)
            DNA methylation patterns are altered in numerous diseases and often correlate with clinically relevant information such as disease subtypes, prognosis and drug response. With suitable assays and after validation in large cohorts, such associations can be exploited for clinical diagnostics and personalized treatment decisions. Here we describe the results of a community-wide benchmarking study comparing the performance of all widely used methods for DNA methylation analysis that are compatible with routine clinical use. We shipped 32 reference samples to 18 laboratories in seven different countries. Researchers in those laboratories collectively contributed 21 locus-specific assays for an average of 27 predefined genomic regions, as well as six global assays. We evaluated assay sensitivity on low-input samples and assessed the assays' ability to discriminate between cell types. Good agreement was observed across all tested methods, with amplicon bisulfite sequencing and bisulfite pyrosequencing showing the best all-round performance. Our technology comparison can inform the selection, optimization and use of DNA methylation assays in large-scale validation studies, biomarker development and clinical diagnostics.
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              From profiles to function in epigenomics

              Myriads of epigenomic features have been comprehensively profiled in health and disease across cell types, tissues and individuals. Although current epigenomic approaches can infer function for chromatin marks through correlation, it remains challenging to establish which marks actually have causative roles in gene regulation and other processes. After revisiting how classical approaches have addressed this question in the past, we discuss the current state of epigenomic profiling and how functional information can be indirectly inferred. We also present new approaches that promise definitive functional answers, which are collectively referred to as 'epigenome editing'. In particular, we explore CRISPR-based technologies for single-locus and multi-locus manipulation. Finally, we discuss which level of function can be achieved with each approach and introduce emerging strategies for high-throughput progression from profiles to function.
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                Author and article information

                Journal
                Cell
                Cell
                Elsevier BV
                00928674
                November 2016
                November 2016
                : 167
                : 5
                : 1145-1149
                Article
                10.1016/j.cell.2016.11.007
                27863232
                48017e8e-f637-4045-855c-66b569bc57ca
                © 2016
                History

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