Enhancer connectome in primary human cells identifies target genes of disease-associated DNA elements

Nature Genetics

Volumn 49, Issue 11, 2017, Pages 1602-1612

  Mumbach, Maxwell R ^a   Satpathy, Ansuman T ^a   Boyle, Evan A ^a   Dai, Chao ^a   Gowen, Benjamin G ^b   Cho, Seung Woo ^a   Nguyen, Michelle L ^c   Rubin, Adam J ^a   Granja, Jeffrey M ^a   Kazane, Katelynn R ^b   Wei, Yuning ^a   Nguyen, Trieu ^a   Greenside, Peyton G ^a   Corces, M Ryan ^a   Tycko, Josh ^a   Simeonov, Dimitre R ^c,d   Suliman, Nabeela ^a   Li, Rui ^a   Xu, Jin ^a   Flynn, Ryan A ^a   Kundaje, Anshul ^a   Khavari, Paul A ^a   Marson, Alexander ^b,c,e   Corn, Jacob E ^b   Quertermous, Thomas ^a   Greenleaf, William J ^a,e,f   Chang, Howard Y ^a   more..

^a STANFORD UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b UNIVERSITY OF CALIFORNIA   (United States)

^c UNIVERSITY OF CALIFORNIA   (United States)

^d UNIVERSITY OF CALIFORNIA   (United States)

^e CHAN ZUCKERBERG BIOHUB   (United States)

^f STANFORD UNIVERSITY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

DNA; CHROMATIN; HISTONE; SPACER DNA;

ALLELE; ANIMAL CELL; ARTERIAL SMOOTH MUSCLE CELL; ARTICLE; AUTOIMMUNE DISEASE; CARDIOVASCULAR DISEASE; CLUSTERED REGULARLY INTERSPACED SHORT PALINDROMIC REPEAT; CONNECTOME; CONTROLLED STUDY; CORONARY ARTERY MUSCLE; ENHANCER REGION; GENE TARGETING; GENETIC DISORDER; HUMAN; HUMAN CELL; LYMPHOCYTE DIFFERENTIATION; MOUSE; NONHUMAN; PRIMARY CELL; PRIORITY JOURNAL; QUANTITATIVE TRAIT LOCUS; REGULATORY T LYMPHOCYTE; TH17 CELL; CELL DIFFERENTIATION; CHROMATIN; CHROMATIN IMMUNOPRECIPITATION; CYTOLOGY; GENETICS; HELPER CELL; HUMAN GENOME; IMMUNOLOGY; K-562 CELL LINE; METABOLISM; MUTATION; PATHOLOGY; PRIMARY CELL CULTURE; PROCEDURES; PROMOTER REGION; SMOOTH MUSCLE CELL;

ALLELES; AUTOIMMUNE DISEASES; CARDIOVASCULAR DISEASES; CELL DIFFERENTIATION; CHROMATIN; CHROMATIN IMMUNOPRECIPITATION; CLUSTERED REGULARLY INTERSPACED SHORT PALINDROMIC REPEATS; DNA, INTERGENIC; ENHANCER ELEMENTS, GENETIC; GENOME, HUMAN; HISTONES; HUMANS; K562 CELLS; MUTATION; MYOCYTES, SMOOTH MUSCLE; PRIMARY CELL CULTURE; PROMOTER REGIONS, GENETIC; QUANTITATIVE TRAIT LOCI; T-LYMPHOCYTES, HELPER-INDUCER; T-LYMPHOCYTES, REGULATORY;

EID: 85032453347     PISSN: 10614036     EISSN: 15461718     Source Type: Journal    
DOI: 10.1038/ng.3963     Document Type: Article

References (60)

1. Dixon, J.R. et al. Topological domains in mammalian genomes identified by analysis of chromatin interactions. Nature 485, 376-380 (2012).
2. van Arensbergen, J., van Steensel, B. & Bussemaker, H.J. In search of the determinants of enhancer-promoter interaction specificity. Trends Cell Biol. 24, 695-702 (2014).
3. Lieberman-Aiden, E. et al. Comprehensive mapping of long-range interactions reveals folding principles of the human genome. Science 326, 289-293 (2009).
4. Rao, S.S.P. et al. A 3D map of the human genome at kilobase resolution reveals principles of chromatin looping. Cell 159, 1665-1680 (2014).
5. Fulco, C.P. et al. Systematic mapping of functional enhancer-promoter connections with CRISPR interference. Science 354, 769-773 (2016).
6. Altshuler, D., Daly, M.J. & Lander, E.S. Genetic mapping in human disease. Science 322, 881-888 (2008).
7. Kumar, V. et al. Human disease-associated genetic variation impacts large intergenic non-coding RNA expression. PLoS Genet. 9, e1003201 (2013).
8. Edwards, S.L., Beesley, J., French, J.D. & Dunning, A.M. Beyond GWASs: illuminating the dark road from association to function. Am. J. Hum. Genet. 93, 779-797 (2013).
9. Welter, D. et al. The NHGRI GWAS Catalog, a curated resource of SNP-trait associations. Nucleic Acids Res. 42, D1001-D1006 (2014).
10. Smemo, S. et al. Obesity-associated variants within FTO form long-range functional connections with IRX3. Nature 507, 371-375 (2014).
11. Claussnitzer, M. et al. FTO obesity variant circuitry and adipocyte browning in humans. N. Engl. J. Med. 373, 895-907 (2015).
12. Grubert, F. et al. Genetic control of chromatin states in humans involves local and distal chromosomal interactions. Cell 162, 1051-1065 (2015).
13. Mifsud, B. et al. Mapping long-range promoter contacts in human cells with high-resolution capture Hi-C. Nat. Genet. 47, 598-606 (2015).
14. Javierre, B.M. et al. Lineage-specific genome architecture links enhancers and non-coding disease variants to target gene promoters. Cell 167, 1369-1384 (2016).
15. Sanjana, N.E. et al. High-resolution interrogation of functional elements in the noncoding genome. Science 353, 1545-1549 (2016).
16. Mumbach, M.R. et al. HiChIP: effcient and sensitive analysis of protein-directed genome architecture. Nat. Methods 13, 919-922 (2016).
17. Heintzman, N.D. et al. Distinct and predictive chromatin signatures of transcriptional promoters and enhancers in the human genome. Nat. Genet. 39, 311-318 (2007).
18. Creyghton, M.P. et al. Histone H3K27ac separates active from poised enhancers and predicts developmental state. Proc. Natl. Acad. Sci. USA 107, 21931-21936 (2010).
19. Rada-Iglesias, A. et al. A unique chromatin signature uncovers early developmental enhancers in humans. Nature 470, 279-283 (2011).
20. Ferraro, A. et al. Interindividual variation in human T regulatory cells. Proc. Natl. Acad. Sci. USA 111, E1111-E1120 (2014).
21. Arvey, A. et al. Genetic and epigenetic variation in the lineage specification of regulatory T cells. eLife 4, e07571 (2015).
22. H17 and regulatory T cells. Nature 441, 235-238 (2006).
23. Acosta-Rodriguez, E.V. et al. Surface phenotype and antigenic specificity of human interleukin 17-producing T helper memory cells. Nat. Immunol. 8, 639-646 (2007).
24. + T cells are counterparts of T follicular cells and contain specific subsets that differentially support antibody secretion. Immunity 34, 108-121 (2011).
25. Farh, K.K.-H. et al. Genetic and epigenetic fne mapping of causal autoimmune disease variants. Nature 518, 337-343 (2015).
26. Simeonov, D.R. et al. Discovery of stimulation-responsive immune enhancers with CRISPR activation. Nature 549, 111-115 (2017).
27. Engreitz, J.M. et al. Local regulation of gene expression by lncRNA promoters, transcription and splicing. Nature 539, 452-455 (2016).
28. Dao, L.T.M. et al. Genome-wide characterization of mammalian promoters with distal enhancer functions. Nat. Genet. 49, 1073-1081 (2017).
29. Ernst, J. & Kellis, M. ChromHMM: automating chromatin-state discovery and characterization. Nat. Methods 9, 215-216 (2012).
30. Sanborn, A.L. et al. Chromatin extrusion explains key features of loop and domain formation in wild-type and engineered genomes. Proc. Natl. Acad. Sci. USA 112, E6456-E6465 (2015).
31. Li, G. et al. Extensive promoter-centered chromatin interactions provide a topological basis for transcription regulation. Cell 148, 84-98 (2012).
32. Buenrostro, J.D., Giresi, P.G., Zaba, L.C., Chang, H.Y. & Greenleaf, W.J. Transposition of native chromatin for fast and sensitive epigenomic profling of open chromatin, DNA-binding proteins and nucleosome position. Nat. Methods 10, 1213-1218 (2013).
33. Samstein, R.M. et al. Foxp3 exploits a pre-existent enhancer landscape for regulatory T cell lineage specification. Cell 151, 153-166 (2012).
34. Ye, C.J. et al. Intersection of population variation and autoimmunity genetics in human T cell activation. Science 345, 1254665 (2014).
35. Petukhova, L. et al. Genome-wide association study in alopecia areata implicates both innate and adaptive immunity. Nature 466, 113-117 (2010).
36. Raj, T. et al. Polarization of the effects of autoimmune and neurodegenerative risk alleles in leukocytes. Science 344, 519-523 (2014).
37. Schiering, C. et al. The alarmin IL-33 promotes regulatory T-cell function in the intestine. Nature 513, 564-568 (2014).
38. Huang, H. et al. Fine-mapping infammatory bowel disease loci to single-variant resolution. Nature 547, 173-178 (2017).
39. Onengut-Gumuscu, S. et al. Fine mapping of type 1 diabetes susceptibility loci and evidence for colocalization of causal variants with lymphoid gene enhancers. Nat. Genet. 47, 381-386 (2015).
40. + T helper cell differentiation. Nat. Rev. Immunol. 11, 239-250 (2011).
41. Miller, C.L. et al. Integrative functional genomics identifes regulatory mechanisms at coronary artery disease loci. Nat. Commun. 7, 12092 (2016).
42. Nurnberg, S.T. et al. Coronary artery disease associated transcription factor TCF21 regulates smooth muscle precursor cells that contribute to the fbrous cap. PLoS Genet. 11, e1005155 (2015).
43. McPherson, R. et al. A common allele on chromosome 9 associated with coronary heart disease. Science 316, 1488-1491 (2007).
44. Helgadottir, A. et al. A common variant on chromosome 9p21 affects the risk of myocardial infarction. Science 316, 1491-1493 (2007).
45. Clarke, R. et al. Genetic variants associated with Lp(a) lipoprotein level and coronary disease. N. Engl. J. Med. 361, 2518-2528 (2009).
46. CARDIoGRAMplusC4D Consortium. Large-scale association analysis identifes new risk loci for coronary artery disease. Nat. Genet. 45, 25-33 (2013).
47. Leung, D. et al. Integrative analysis of haplotype-resolved epigenomes across human tissues. Nature 518, 350-354 (2015).
48. Dixon, J.R. et al. Chromatin architecture reorganization during stem cell differentiation. Nature 518, 331-336 (2015).
49. Franzén, O. et al. Cardiometabolic risk loci share downstream cis- and trans-gene regulation across tissues and diseases. Science 353, 827-830 (2016).
50. Sinha, R. et al. Index switching causes "spreading-of-signal" among multiplexed samples in Illumina HiSeq 4000 DNA sequencing. Preprint at bioRxiv http://dx. doi.org/10.1101/125724 (2017).
51. Servant, N. et al. HiC-Pro: an optimized and fexible pipeline for Hi-C data processing. Genome Biol. 16, 259 (2015).
52. Gjoneska, E. et al. Conserved epigenomic signals in mice and humans reveal immune basis of Alzheimer's disease. Nature 518, 365-369 (2015).
53. Kagey, M.H. et al. Mediator and cohesin connect gene expression and chromatin architecture. Nature 467, 430-435 (2010).
54. Yue, F. et al. A comparative encyclopedia of DNA elements in the mouse genome. Nature 515, 355-364 (2014).
55. Bonnal, R.J.P. et al. De novo transcriptome profling of highly purifed human lymphocytes primary cells. Sci. Data 2, 150051 (2015).
56. Adamson, B. et al. A multiplexed single-cell CRISPR screening platform enables systematic dissection of the unfolded protein response. Cell 167, 1867-1882 (2016).
57. Gilbert, L.A. et al. Genome-scale CRISPR-mediated control of gene repression and activation. Cell 159, 647-661 (2014).
58. Doench, J.G. et al. Optimized sgRNA design to maximize activity and minimize off-target effects of CRISPR-Cas9. Nat. Biotechnol. 34, 184-191 (2016).
59. Hsu, P.D. et al. DNA targeting specificity of RNA-guided Cas9 nucleases. Nat. Biotechnol. 31, 827-832 (2013).
60. Horlbeck, M.A. et al. Nucleosomes impede Cas9 access to DNA in vivo and in vitro. eLife 5, e12677 (2016).