CER ENHAN
M
eD
IP
Illustration by Nik Spencer/Nature
CONTENTS OTER PROM
DNase1
NEWS & VIEWS
314 Roadmap for regulation
C E Romanoski & C K Glass; H G Stunnenberg; L Wilson & G Almouzni
ARTICLES
RNA pol
317 Integrative analysis of 111 reference
human epigenomes Roadmap Epigenomics Consortium et al.
331 Chromatin architecture reorganization during stem cell differentiation J R Dixon et al.
A pol RN
A RN
337 Genetic and epigenetic fine mapping of causal autoimmune disease variants K K-H Farh et al.
l po
344 Transcription factor binding dynamics during human ES cell differentiation A M Tsankov et al.
EPIGENOME ROADMAP E
LETTERs
350 Integrative analysis of haplotype-
EN pigenetics is implicated not just in the normal functioning of a cell and development but HA CE also inNdisease. Availability of the human genome sequence was a prerequisite for studies R of genetic variation and its association with disease. The NIH Roadmap Epigenomics Program was created to provide a similar reference for genome-wide analyses of epigenetic ER PROMOT changes — the epigenome. The result is a public data resource containing information on DNA methylation, histone modifications, chromatin accessibility and small RNAs in stem cells and primary cell lines selected to represent tissues and organs frequently involved in disease. This effort now culminates in the publication — here and elsewhere — of a considerable body of research papers. On page 317 of this issue, the Roadmap Epigenomics Consortium describes the integrative analysis of 111 reference human epigenomes generated to establish global maps of regulatory elements. On page 350, Ren and colleagues describe the first human haplotype–resolved epigenomes, and show how they vary across tissues and among individuals. Bernstein, Hafler and colleagues (page 337) present a fine-mapping strategy for genetic and epigenetic causal variants in 21 autoimmune diseases. On page 365, Tsai, Kellis and colleagues describe and compare hippocampal epigenomes of Alzheimer’s disease patients with those of relevant mouse models. Stamatoyannopoulos, Sunyaev and colleagues (page 360) show how cell-of-origin chromatin organization shapes the mutational landscape of cancer. Finally, three papers (pages 344, 355 and 331) dissect the role of epigenetic regulation in stem cell differentiation. Meissner and colleagues describe context-dependent rewiring of transcriptional regulation during differentiation of stem cells; Elkabetz, Meissner and colleagues studied regulatory networks during neural differentiation; while Ren and colleagues describe chromatin architecture changes during stem cell differentiation. Research in this issue is accompanied by an online collection — the Epigenome Roadmap — which unites research from across Nature Publishing Group journals, as well as news stories and multimedia. Exploration of research papers is enhanced by ‘threads’, which highlight topics discussed in more than one paper. We acknowledge the exclusive financial support of Illumina in producing this online collection. As always, Nature has full responsibility for all editorial content.
Magdalena Skipper Senior Editor (coordinating editor) Alex Eccleston Senior Editor Noah Gray Senior Editor Therese Heemels Senior Editor
TATA
resolved epigenomes across human tissues D Leung et al.
355 Dissecting neural differentiation regulatory networks through epigenetic footprinting M J Ziller et al.
360 Cell-of-origin chromatin organization shapes the mutational landscape of cancer P Polak et al.
365 Conserved epigenomic signals in mice and humans reveal immune basis of Alzheimer’s disease E Gjoneska et al.
More online n at u r e e p i g e n om e r oa dm a p Epigenome Roadmap offers you a way of exploring a wealth of data from across Nature Publishing Group journals. By linking relevant paragraphs, figures and tables from all 24 papers in the collection, the ‘threads’ allow you to examine different themes.
www.nature.com/epigenomeroadmap
Nathalie Le Bot Senior Editor Barbara Marte Senior Editor Ursula Weiss Senior Editor
1 9 F e b r u a r y 2 0 1 5 | V O L 5 1 8 | N A T URE | 3 1 3
M
eD
IP
Illustration by Nik Spencer/Nature
CONTENTS OTER PROM
DNase1
NEWS & VIEWS
314 Roadmap for regulation
C E Romanoski & C K Glass; H G Stunnenberg; L Wilson & G Almouzni
ARTICLES
RNA pol
317 Integrative analysis of 111 reference
human epigenomes Roadmap Epigenomics Consortium et al.
331 Chromatin architecture reorganization during stem cell differentiation J R Dixon et al.
A pol RN
A RN
337 Genetic and epigenetic fine mapping of causal autoimmune disease variants K K-H Farh et al.
l po
344 Transcription factor binding dynamics during human ES cell differentiation A M Tsankov et al.
EPIGENOME ROADMAP E
LETTERs
350 Integrative analysis of haplotype-
EN pigenetics is implicated not just in the normal functioning of a cell and development but HA CE also inNdisease. Availability of the human genome sequence was a prerequisite for studies R of genetic variation and its association with disease. The NIH Roadmap Epigenomics Program was created to provide a similar reference for genome-wide analyses of epigenetic ER PROMOT changes — the epigenome. The result is a public data resource containing information on DNA methylation, histone modifications, chromatin accessibility and small RNAs in stem cells and primary cell lines selected to represent tissues and organs frequently involved in disease. This effort now culminates in the publication — here and elsewhere — of a considerable body of research papers. On page 317 of this issue, the Roadmap Epigenomics Consortium describes the integrative analysis of 111 reference human epigenomes generated to establish global maps of regulatory elements. On page 350, Ren and colleagues describe the first human haplotype–resolved epigenomes, and show how they vary across tissues and among individuals. Bernstein, Hafler and colleagues (page 337) present a fine-mapping strategy for genetic and epigenetic causal variants in 21 autoimmune diseases. On page 365, Tsai, Kellis and colleagues describe and compare hippocampal epigenomes of Alzheimer’s disease patients with those of relevant mouse models. Stamatoyannopoulos, Sunyaev and colleagues (page 360) show how cell-of-origin chromatin organization shapes the mutational landscape of cancer. Finally, three papers (pages 344, 355 and 331) dissect the role of epigenetic regulation in stem cell differentiation. Meissner and colleagues describe context-dependent rewiring of transcriptional regulation during differentiation of stem cells; Elkabetz, Meissner and colleagues studied regulatory networks during neural differentiation; while Ren and colleagues describe chromatin architecture changes during stem cell differentiation. Research in this issue is accompanied by an online collection — the Epigenome Roadmap — which unites research from across Nature Publishing Group journals, as well as news stories and multimedia. Exploration of research papers is enhanced by ‘threads’, which highlight topics discussed in more than one paper. We acknowledge the exclusive financial support of Illumina in producing this online collection. As always, Nature has full responsibility for all editorial content.
Magdalena Skipper Senior Editor (coordinating editor) Alex Eccleston Senior Editor Noah Gray Senior Editor Therese Heemels Senior Editor
TATA
resolved epigenomes across human tissues D Leung et al.
355 Dissecting neural differentiation regulatory networks through epigenetic footprinting M J Ziller et al.
360 Cell-of-origin chromatin organization shapes the mutational landscape of cancer P Polak et al.
365 Conserved epigenomic signals in mice and humans reveal immune basis of Alzheimer’s disease E Gjoneska et al.
More online n at u r e e p i g e n om e r oa dm a p Epigenome Roadmap offers you a way of exploring a wealth of data from across Nature Publishing Group journals. By linking relevant paragraphs, figures and tables from all 24 papers in the collection, the ‘threads’ allow you to examine different themes.
www.nature.com/epigenomeroadmap
Nathalie Le Bot Senior Editor Barbara Marte Senior Editor Ursula Weiss Senior Editor
1 9 F e b r u a r y 2 0 1 5 | V O L 5 1 8 | N A T URE | 3 1 3
