An atlas of active enhancers across human cell types and tissues

Nature

Volumn 507, Issue 7493, 2014, Pages 455-461

  Andersson, Robin ^a   Gebhard, Claudia ^b,c   Miguel Escalada, Irene ^d   Hoof, Ilka ^a   Bornholdt, Jette ^a   Boyd, Mette ^a   Chen, Yun ^a   Zhao, Xiaobei ^a,e   Schmidl, Christian ^b   Suzuki, Takahiro ^f   Ntini, Evgenia ^g   Arner, Erik ^f   Valen, Eivind ^a,h   Li, Kang ^a   Schwarzfischer, Lucia ^b   Glatz, Dagmar ^b   Raithel, Johanna ^b   Lilje, Berit ^a   Rapin, Nicolas ^a,i   Bagger, Frederik Otzen ^a,i   Jørgensen, Mette ^a   Andersen, Peter Refsing ^g   Bertin, Nicolas ^f   Rackham, Owen ^f   Burroughs, A Maxwell ^f   Baillie, J Kenneth ^j   Ishizu, Yuri ^f   Shimizu, Yuri ^f   Furuhata, Erina ^f   Maeda, Shiori ^f   Negishi, Yutaka ^f   Mungall, Christopher J ^k   Meehan, Terrence F ^l   Lassmann, Timo ^f   Itoh, Masayoshi ^f   Kawaji, Hideya ^f   Kondo, Naoto ^f   Kawai, Jun ^f   Lennartsson, Andreas ^m   Daub, Carsten O ^f,m   Heutink, Peter ⁿ   Hume, David A ^j   Jensen, Torben Heick ^g   Suzuki, Harukazu ^f   Hayashizaki, Yoshihide ^f   Müller, Ferenc ^d   Forrest, Alistair R R ^f   Carninci, Piero ^f   Rehli, Michael ^b,c   Sandelin, Albin ^a   more..

^a UNIVERSITY OF COPENHAGEN   (Denmark)

^b UNIVERSITY HOSPITAL REGENSBURG   (Germany)

^c Regensburg Centre for Interventional Immunology (RCI)   (Germany)

^d UNIVERSITY OF BIRMINGHAM   (United Kingdom)

^e UNIVERSITY OF NORTH CAROLINA   (United States)

^f RIKEN YOKOHAMA INSTITUTE   (Japan)

^g Building 1130 ^*  (Denmark)

^h HARVARD UNIVERSITY   (United States)

ⁱ UNIVERSITY OF COPENHAGEN   (Denmark)

^j UNIVERSITY OF EDINBURGH   (United Kingdom)

^k LAWRENCE BERKELEY NATIONAL LABORATORY   (United States)

^l WELLCOME TRUST SANGER INSTITUTE   (United Kingdom)

^m KAROLINSKA INSTITUTE   (Sweden)

ⁿ VU UNIVERSITY MEDICAL CENTER   (Netherlands)

more..

Author keywords

[No Author keywords available]

Indexed keywords

MESSENGER RNA;

GENE EXPRESSION; GENETIC ANALYSIS; GENOME; HOMEOSTASIS; POLYMORPHISM; RNA;

ARTICLE; CELL FATE; CELL SPECIFICITY; CELL TYPE; ENHANCER REGION; EXOSOME; GENE CONTROL; GENE EXPRESSION; HOMEOSTASIS; HUMAN; HUMAN CELL; HUMAN TISSUE; IN VIVO CULTURE; NONHUMAN; NUCLEOTIDE SEQUENCE; PRIORITY JOURNAL; SINGLE NUCLEOTIDE POLYMORPHISM; TISSUES; ZEBRA FISH;

ATLASES AS TOPIC; CELL LINE; CELLS, CULTURED; CLUSTER ANALYSIS; ENHANCER ELEMENTS, GENETIC; GENE EXPRESSION REGULATION; GENETIC PREDISPOSITION TO DISEASE; HELA CELLS; HUMANS; MOLECULAR SEQUENCE ANNOTATION; ORGAN SPECIFICITY; POLYMORPHISM, SINGLE NUCLEOTIDE; PROMOTER REGIONS, GENETIC; RNA, MESSENGER; TRANSCRIPTION INITIATION SITE; TRANSCRIPTION INITIATION, GENETIC;

EID: 84897459814     PISSN: 00280836     EISSN: 14764687     Source Type: Journal    
DOI: 10.1038/nature12787     Document Type: Article

References (74)

1. Bulger, M. & Groudine, M. Enhancers: the abundance and function of regulatory sequences beyond promoters. Dev. Biol. 339, 250-257 (2010).
2. Lenhard, B., Sandelin, A. & Carninci, P. Metazoan promoters: emerging characteristics and insights into transcriptional regulation. Nature Rev. Genet. 13, 233-245 (2012).
3. Banerji, J., Rusconi,S.&Schaffner, W. Expression of a b-globin gene isenhanced by remote SV40 DNA sequences. Cell 27, 299-308 (1981).
4. Kim, T.-K. et al. Widespread transcription at neuronal activity-regulated enhancers. Nature 465, 182-187 (2010).
5. Kodzius, R. et al. CAGE: cap analysis of gene expression. Nature Methods 3, 211-222 (2006).
6. The FANTOM Consortium and the RIKEN PMI and CLST (DGT). A promoter-level mammalian expression atlas. Nature http://dx.doi.org/10.1038/nature13182 (this issue).
7. The ENCODE Project Consortium. An integrated encyclopedia of DNA elements in the human genome. Nature 489, 57-74 (2012).
8. Kheradpour, P. et al. Systematic dissection of regulatory motifs in 2000 predicted human enhancers using a massively parallel reporter assay. Genome Res. 23, 800-811 (2013).
9. Fort, A. et al. Deep transcriptome profiling of mammalian stem cells supports a regulatory role for retrotransposons in pluripotency maintenance. Nature Genet. (in the press).
10. Thurman, R. E. et al. The accessible chromatin landscape of the human genome. Nature 489, 75-82 (2012).
11. Ntini, E. et al.Polyadenylationsite-induced decay ofupstreamtranscripts enforces promoter directionality. Nature Struct. Mol. Biol. 20, 923-928 (2013).
12. Almada, A. E., Wu, X., Kriz, A. J., Burge, C. B. & Sharp, P. A. Promoter directionality is controlled byU1snRNP and polyadenylationsignals. Nature 499, 360-363 (2013).
13. Djebali, S. et al. Landscape of transcription in human cells. Nature 489, 101-108 (2012).
14. Kowalczyk, M. S. et al. Intragenic enhancers act as alternative promoters. Mol. Cell 45, 447-458 (2012).
15. Valen, E. et al. Biogenic mechanisms and utilization of small RNAs derived from human protein-coding genes. Nature Struct. Mol. Biol. 18, 1075-1082 (2011).
16. Taft, R. J. et al. TinyRNAs associated with transcription start sites in animals. Nature Genet. 41, 572-578 (2009).
17. Core, L. J., Waterfall, J. J. & Lis, J. T. Nascent RNA sequencing reveals widespread pausing and divergent initiation at human promoters. Science 322, 1845-1848 (2008).
18. Rönnerblad, M. et al. Analysis of the DNA methylome and transcriptome in granulopoiesis reveal timed changes and dynamic enhancer methylation. Blood http://dx.doi.org/10.1182/blood-2013-02-482893 (in the press).
19. Biddie, S. C. et al. Transcription factor AP1 potentiates chromatin accessibility and glucocorticoid receptor binding. Mol. Cell 43, 145-155 (2011).
20. Schmidt, D. et al. A CTCF-independent role for cohesin in tissue-specific transcription. Genome Res. 20, 578-588 (2010).
21. Li, G. et al. Extensive promoter-centered chromatin interactions provide a topological basis for transcription regulation. Cell 148, 84-98 (2012).
22. Chepelev, I., Wei, G., Wangsa, D., Tang, Q. & Zhao, K. Characterization of genome-wide enhancer-promoter interactions reveals co-expression of interacting genes and modes of higher order chromatin organization. Cell Res. 22, 490-503 (2012).
23. Fraser, P., Pruzina, S., Antoniou, M. & Grosveld, F. Each hypersensitive site of the human beta-globin locus control region confers a different developmental pattern of expression on the globin genes. Genes Dev. 7, 106-113 (1993).
24. Dostie, J. et al. Chromosome Conformation Capture Carbon Copy (5C): A massively parallel solution for mapping interactions between genomic elements. Genome Res. 16, 1299-1309 (2006).
25. Barolo, S. Shadow enhancers: frequently asked questions about distributed cis-regulatory information and enhancer redundancy. Bioessays 34, 135-141 (2012).
26. Schaffner, G., Schirm, S., Müller-Baden, B., Weber, F. & Schaffner, W. Redundancy of information in enhancers as a principle of mammalian transcription control. J. Mol. Biol. 201, 81-90 (1988).
27. Whyte, W. A. et al. Master transcription factors and mediator establish super-enhancers at key cell identity genes. Cell 153, 307-319 (2013).
28. Göring, H. H. H. et al. Discovery of expressionQTLs using large-scale transcriptional profiling in human lymphocytes. Nature Genet. 39, 1208-1216 (2007).
29. Hindorff, L. A. et al. Potential etiologic and functional implications of genome-wide association loci for human diseases and traits. Proc. Natl Acad. Sci. USA 106, 9362-9367 (2009).
30. Ward, L. D. & Kellis, M. HaploReg: a resource for exploring chromatin states, conservation, and regulatory motif alterations within sets of genetically linked variants. Nucleic Acids Res. 40, D930-D934 (2012).
31. Maurano, M. T., Wang, H., Kutyavin, T. & Stamatoyannopoulos, J. A. Widespread site-dependent buffering of human regulatory polymorphism. PLoS Genet. 8, e1002599 (2012).
32. Mercer, E. M. et al. Multilineage priming of enhancer repertoires precedes commitment to the B and myeloid cell lineages in hematopoietic progenitors. Immunity 35, 413-425 (2011).
33. Ostuni, R. et al. Latent enhancers activated by stimulation in differentiated cells. Cell 152, 157-171 (2013).
34. Rada-Iglesias, A. et al.Auniquechromatin signature uncovers early developmental enhancers in humans. Nature 470, 279-283 (2011).
35. Shen, Y. et al. A map of the cis-regulatory sequences in the mouse genome. Nature 488, 116-120 (2012).
36. Heinz, S. et al. Simple combinations of lineage-determining transcription factors prime cis-regulatory elements required for macrophage and B cell identities. Mol. Cell 38, 576-589 (2010).
37. Friedman, J., Hastie, T. & Tibshirani, R. Regularization paths for generalized linear models via coordinate descent. J. Stat. Softw. 33, 1-22 (2010).
38. Gehrig, J. et al. Automated high-throughput mapping of promoter-enhancer interactions in zebrafish embryos. Nature Methods 6, 911-916 (2009).
39. Kanamori-Katayama, M. et al. Unamplified cap analysis of gene expression on a single-molecule sequencer. Genome Res. 21, 1150-1159 (2011).
40. Khalil, A. M. et al. Many human large intergenic noncoding RNAs associate with chromatin-modifying complexes and affect gene expression. Proc. Natl Acad. Sci. USA 106, 11667-11672 (2009).
41. Robinson, M. D., McCarthy, D. J. & Smyth, G. K., Edge R: A Bioconductor package for differential expression analysis of digital gene expression data. Bioinformatics 26, 139-140 (2010).
42. Hoffman, M. M. et al. Unsupervised pattern discovery in human chromatin structure through genomic segmentation. Nature Methods 9, 473-476 (2012).
43. Ernst, J. & Kellis, M. Chrom HMM: Automating chromatin-state discovery and characterization. Nature Methods 9, 215-216 (2012).
44. Heintzman, N. D. et al. Histone modifications at human enhancers reflect global cell-type-specific gene expression. Nature 459, 108-112 (2009).
45. Marshall, O. J. PerlPrimer: cross-platform, graphical primer design for standard, bisulphite and real-time PCR. Bioinformatics 20, 2471-2472 (2004).
46. Trapnell, C., Pachter, L. & Salzberg, S. L. TopHat: discovering splice junctions with RNA-Seq. Bioinformatics 25, 1105-1111 (2009).
47. Trapnell, C. et al. Transcript assembly and quantification by RNA-Seq reveals unannotated transcripts and isoform switching during cell differentiation. Nature Biotechnol. 28, 511-515 (2010).
48. Preker, P. et al. RNA exosome depletion reveals transcription upstream of active human promoters. Science 322, 1851-1854 (2008).
49. Takahashi, H., Lassmann, T., Murata, M. & Carninci, P. 59 end-centered expression profiling using cap-analysis gene expression and next-generation sequencing. Nature Protocols 7, 542-561 (2012).
50. Langmead, B., Trapnell, C., Pop, M.&Salzberg, S. L. Ultrafast andmemory-efficient alignment of short DNA sequences to the human genome. Genome Biol. 10, R25 (2009).
51. Carninci, P. et al. Genome-wide analysis ofmammalian promoter architecture and evolution. Nature Genet. 38, 626-635 (2006).
52. Pham, T. H. et al. Dynamic epigenetic enhancer signatures reveal key transcription factors associated with monocytic differentiation states. Blood 119, e161-e171 (2012).
53. Zhang, Y. et al. Model-based analysis of ChIP-Seq (MACS). Genome Biol. 9, R137 (2008).
54. Schmidl, C. et al. Lineage-specific DNA methylation in T cells correlates with histone methylation and enhancer activity. Genome Res. 19, 1165-1174 (2009).
55. Klug, M.&Rehli, M. Functional analysis of promoter CpGmethylation using a CpGfree luciferase reporter vector. Epigenetics 1, 127-130 (2006).
56. Rehli, M. et al. PU.1 and interferon consensus sequence-binding protein regulate the myeloid expression of the human Toll-like receptor 4 gene. J. Biol. Chem. 275, 9773-9781 (2000).
57. Li, L. C. & Dahiya, R. MethPrimer: designing primers for methylation PCRs. Bioinformatics 18, 1427-1431 (2002).
58. Ehrich, M. et al. Quantitative high-throughput analysis of DNA methylation patterns by base-specific cleavage and mass spectrometry. Proc. Natl Acad. Sci. USA 102, 15785-15790 (2005).
59. Lin, J. Divergence measures based on the Shannon entropy. IEEE Trans. Inf. Theory 37, 145-151 (1991).
60. Hollander, M. & Wolfe, D. A. Nonparametric Statistical Methods (Wiley-Interscience, 1999).
61. Hothorn, T., Hornik, K., Van De Wiel, M. A.& Zeileis, A. A Lego systemfor conditional inference. Am. Stat. 60, 257-263 (2006).
62. Buckner, J. et al.The gputoolspackage enablesGPUcomputing in R. Bioinformatics 26, 134-135 (2010).
63. Ellingsen, S. et al. Large-scale enhancer detection in the zebrafish genome. Development 132, 3799-3811 (2005).
64. Meng, A., Tang, H., Ong, B. A., Farrell, M. J. & Lin, S. Promoter analysis in living zebrafishembryos identifies a cis-actingmotif required for neuronal expression of GATA-2. Proc. Natl Acad. Sci. USA 94, 6267-6272 (1997).
65. Westerfield, M. The Zebrafish Book. A Guide for the Laboratory Use of Zebrafish (Danio rerio). (Univ. Oregon Press, 1995).
66. Huang, D. W., Sherman, B. T. & Lempicki, R. A. Systematic and integrative analysis of large genelists usingDAVIDbioinformatics resources.Nature Protocols 4,44-57 (2008).
67. Zuber, V.&Strimmer, K. High-dimensional regression and variable selection using CAR scores. Stat. Appl. Genet. Mol. Biol. 10, 1-27 (2011).
68. Chevan, A. & Sutherland, M. Hierarchical partitioning. Am. Stat. 45, 90-96 (1991).
69. Groemping, U. Relative importance for linear regression in R: the package relaimpo. J. Stat. Softw. 17, 1-27 (2006).
70. Johnson, A. D. et al. SNAP: a web-based tool for identification and annotation of proxy SNPs using HapMap. Bioinformatics 24, 2938-2939 (2008).
71. The 1000 Genomes Project Consortium. A map of human genome variation from population-scale sequencing. Nature 467, 1061-1073 (2010).
72. Rhead, B. et al. The UCSC Genome Browser database: update 2010. Nucleic Acids Res. 38, D613-D619 (2010).
73. Paradis, E., Claude, J. & Strimmer, K. APE: analyses of phylogenetics and evolution in R language. Bioinformatics 20, 289-290 (2004).
74. Quinlan, A. R. & Hall, I. M. BEDTools: a flexible suite of utilities for comparing genomic features. Bioinformatics 26, 841-842 (2010).