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Baldridge, M. T., King, K. Y., Boles, N. C., Weksberg, D. C. & Goodell, M. A. \ Quiescent haematopoietic stem cells are activated by IFN- in response to chronic infection. Nature 465, 793 797 \(2010\).\r\ :2549)/F 4/H/N/Rect[95.9842 254.706 101.189 242.16]/Subtype/Link/Type/Annot>> endobj 4 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatImmun_184.indd: 42. Zhao, J. L. et al. Conversion of danger signals into cytokine signals by hemat\ opoietic stem and progenitor cells for regulation of stress-induced hematopoiesis. Cell Stem Cell 14, 445 459 \(2014\).\r:25\ 50)/F 4/H/N/Rect[104.008 254.706 109.213 242.16]/Subtype/Link/Type/Annot>> endobj 5 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatImmun_184.indd: 28. Ley, T. J. et al. Cancer Genome Atlas Research Network. Genomic and epigenomic\ landscapes of adult de novo acute myeloid leukemia. N. Engl. J. 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Bennett, J. M. et al. Proposals for the classification of the acute leukaemias\ . Br. J. Haematol. 33, 451 458 \(1976\).\r:2556)/F 4/H/N/Rect[61.9746 55.2059 67.1796 42.6602]/Subtype/Link/Type/Annot>> endobj 10 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatImmun_184.indd:Fig. 1 | Cohesin links inflammation and cancer. a, Analysis of RNA-seq dat\ a from 173 primary human TCGA cases of AML, 23 of which had missense or truncating mutations in the cohesin genes RAD21, SMC3\ , SMC1A or STAG2, showed sign:2557)/F 4/H/N/Rect[447.84 213.32 457.214 199.277]/Subtype/Link/Type/Annot>> endobj 11 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatImmun_184.indd: 21. Kaikkonen, M. U. et al. Remodeling of the enhancer landscape during macropha\ ge activation is coupled to enhancer transcription. Mol. Cell 51, 310 325 \(2013\).\r:2558)/F 4/H/N/Rect[489.343 118.206 494.547 105.66]/Subtype/Link/Type/Annot>> endobj 12 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatImmun_184.indd: 25. Glass, C. K. & Natoli, G. Molecular control of activation and priming in mac\ rophages. Nat. Immunol. 17, 26 33 \(2016\).\r:2559)/F 4/H/N/Rect[497.367 118.206 502.572 105.66]/Subtype/Link/Type/Annot>> endobj 13 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatImmun_184.indd: 23. Bhatt, D. M. et al. Transcript dynamics of proinflammatory genes \nrevealed by \ sequence analysis of subcellular RNA fractions. 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Seitan, V. C. et al. A role for cohesin in T-cell-receptor rearrangement and\ thymocyte differentiation. Nature 476, 467 471 \(2011\).\r:2560)/F 4/H/N/Rect[286.433 716.706 291.638 704.16]/Subtype/Link/Type/Annot>> endobj 35 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatImmun_184.indd: 30. Mazumdar, C. et al. Leukemia-associated cohesin mutants dominantly enforce s\ tem cell programs and impair human hematopoietic progenitor differentiation. Cell Stem Cell 17, 675 688 \(2015\).\r:2561)/F 4/H/N/Rect[142.557 685.206 147.762 672.66]/Subtype/Link/Type/Annot>> endobj 36 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatImmun_184.indd: 34. Fisher, J. B. et al. The cohesin subunit Rad21 is a negative regulator of he\ matopoietic self-renewal through epigenetic repression of Hoxa7 and Hoxa9. Leukemia 31, 712 719 \(2017\).\r:2562)/F 4/H/N/Rect[150.582 685.206 155.787 672.66]/Subtype/Link/Type/Annot>> endobj 37 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatImmun_184.indd:Fig. 2 | Cohesin promotes inducible gene expression. a, Immunoblot analysis o\ f RAD21 protein expression in mature macrophages after Rad21 deletion \(mean 13.6% of control, 13 biological replicates\). b,\ Regulation of inducible genes at b:2563)/F 4/H/N/Rect[62.7172 632.706 71.2639 620.16]/Subtype/Link/Type/Annot>> endobj 38 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatImmun_184.indd: 2. Nora, E. P. et al. Targeted degradation of CTCF decouples local insulation of\ chromosome domains from genomic compartmentalization. Cell 169, 930 944.e22 \(2017\).\r:2564)/F 4/H/N/Rect[125.413 632.706 128.016 620.16]/Subtype/Link/Type/Annot>> endobj 39 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatImmun_184.indd: 4. Rao, S. S. P. et al. Cohesin loss eliminates all loop domains. Cell 171, \ 305 320.e24 \(2017\).\r:2565)/F 4/H/N/Rect[129.252 632.706 131.854 620.16]/Subtype/Link/Type/Annot>> endobj 40 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatImmun_184.indd: 7. Schwarzer, W. et al. Two independent modes of chromatin organization reveale\ d by cohesin removal. Nature 551, 51 56 \(2017\).\r:2566)/F 4/H/N/Rect[133.091 632.706 135.693 620.16]/Subtype/Link/Type/Annot>> endobj 41 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatImmun_184.indd: 17. Seitan, V. C. et al. A role for cohesin in T-cell-receptor rearrangement an\ d thymocyte differentiation. Nature 476, 467 471 \(2011\).\r:2567)/F 4/H/N/Rect[136.929 632.706 142.134 620.16]/Subtype/Link/Type/Annot>> endobj 42 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatImmun_184.indd:Fig. 2 | Cohesin promotes inducible gene expression. a, Immunoblot analysis \ of RAD21 protein expression in mature macrophages after Rad21 deletion \(mean 13.6% of control, 13 biological replicates\). b\ , Regulation of inducible genes at :2568)/F 4/H/N/Rect[239.336 612.32 248.525 598.277]/Subtype/Link/Type/Annot>> endobj 43 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatImmun_184.indd: 23. Bhatt, D. M. et al. Transcript dynamics of proinflammatory genes \nrevealed by\ sequence analysis of subcellular RNA fractions. Cell 150, \n279 290 \(2012\).\r:2569)/F 4/H/N/Rect[229.277 601.206 234.482 588.66]/Subtype/Link/Type/Annot>> endobj 44 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatImmun_184.indd:Fig. 2 | Cohesin promotes inducible gene expression. a, Immunoblot analysis\ of RAD21 protein expression in mature macrophages after Rad21 deletion \(mean 13.6% of control, 13 biological replicates\). b\ , Regulation of inducible genes at:2570)/F 4/H/N/Rect[258.339 601.206 267.527 588.66]/Subtype/Link/Type/Annot>> endobj 45 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatImmun_184.indd:Fig. 2 | Cohesin promotes inducible gene expression. a, Immunoblot analysi\ s of RAD21 protein expression in mature macrophages after Rad21 deletion \(mean 13.6% of control, 13 biological replicates\). \ b, Regulation of inducible genes a:2571)/F 4/H/N/Rect[93.9473 569.706 102.345 557.16]/Subtype/Link/Type/Annot>> endobj 46 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatImmun_184.indd: 23. Bhatt, D. M. et al. Transcript dynamics of proinflammatory genes \nreveale\ d by sequence analysis of subcellular RNA fractions. Cell 150, \n279 290 \(2012\).\r:2577)/F 4/H/N/Rect[204.651 538.206 209.856 525.66]/Subtype/Link/Type/Annot>> endobj 47 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatImmun_184.indd: 23. Bhatt, D. M. et al. Transcript dynamics of proinflammatory genes \nreveal\ ed by sequence analysis of subcellular RNA fractions. Cell 150, \n279 290 \(2012\).\r:2578)/F 4/H/N/Rect[172.225 506.706 177.43 494.16]/Subtype/Link/Type/Annot>> endobj 48 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatImmun_184.indd:Fig. 2 | Cohesin promotes inducible gene expression. a, Immunoblot analys\ is of RAD21 protein expression in mature macrophages after Rad21 deletion \(mean 13.6% of control, 13 biological replicates\). \ b, Regulation of inducible genes :2579)/F 4/H/N/Rect[202.494 506.706 211.682 494.16]/Subtype/Link/Type/Annot>> endobj 49 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatImmun_184.indd:Fig. 2 | Cohesin promotes inducible gene expression. a, Immunoblot analy\ sis of RAD21 protein expression in mature macrophages after Rad21 deletion \(mean 13.6% of control, 13 biological replicates\).\ b, Regulation of inducible genes:2580)/F 4/H/N/Rect[62.2787 475.206 77.7073 462.66]/Subtype/Link/Type/Annot>> endobj 50 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatImmun_184.indd: 23. Bhatt, D. M. et al. Transcript dynamics of proinflammatory genes \nrevea\ led by sequence analysis of subcellular RNA fractions. Cell 150, \n279 290 \(2012\).\r:2581)/F 4/H/N/Rect[191.649 475.206 196.854 462.66]/Subtype/Link/Type/Annot>> endobj 51 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatImmun_184.indd: 24. Chen, X. et al. Requirement for the histone deacetylase Hdac3 for the inflamma\ tory gene expression program in macrophages. Proc. Natl Acad. Sci. USA 109, E2865 E2874 \(2012\).\r:2582)/F 4/H/N/Rect[110.213 464.706 115.418 452.16]/Subtype/Link/Type/Annot>> endobj 52 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatImmun_184.indd: 24. Chen, X. et al. Requirement for the histone deacetylase Hdac3 for the inflamm\ atory gene expression program in macrophages. Proc. Natl Acad. Sci. USA 109, E2865 E2874 \(2012\).\r:2583)/F 4/H/N/Rect[63.1652 454.206 68.3702 441.66]/Subtype/Link/Type/Annot>> endobj 53 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatImmun_184.indd:Fig. 2 | Cohesin promotes inducible gene expression. a, Immunoblot anal\ ysis of RAD21 protein expression in mature macrophages after Rad21 deletion \(mean 13.6% of control, 13 biological replicates\)\ . b, Regulation of inducible gene:2584)/F 4/H/N/Rect[171.657 401.706 180.185 389.16]/Subtype/Link/Type/Annot>> endobj 54 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatImmun_184.indd: 21. Kaikkonen, M. U. et al. Remodeling of the enhancer landscape during macrop\ hage activation is coupled to enhancer transcription. Mol. Cell 51, 310 325 \(2013\).\r:2585)/F 4/H/N/Rect[92.1348 360.32 97.4048 346.277]/Subtype/Link/Type/Annot>> endobj 55 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatImmun_184.indd: 25. Glass, C. K. & Natoli, G. Molecular control of activation and priming in m\ acrophages. Nat. Immunol. 17, 26 33 \(2016\).\r:2586)/F 4/H/N/Rect[100.257 360.32 105.527 346.277]/Subtype/Link/Type/Annot>> endobj 56 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatImmun_184.indd: 23. Bhatt, D. M. et al. Transcript dynamics of proinflammatory genes \nreve\ aled by sequence analysis of subcellular RNA fractions. Cell 150, \n279 290 \(2012\).\r:2587)/F 4/H/N/Rect[276.289 307.206 281.494 294.66]/Subtype/Link/Type/Annot>> endobj 57 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatImmun_184.indd: 25. Glass, C. K. & Natoli, G. Molecular control of activation and priming in \ macrophages. Nat. Immunol. 17, 26 33 \(2016\).\r:2588)/F 4/H/N/Rect[284.313 307.206 289.518 294.66]/Subtype/Link/Type/Annot>> endobj 58 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatImmun_184.indd:Fig. 2 | Cohesin promotes inducible gene expression. a, Immunoblot ana\ lysis of RAD21 protein expression in mature macrophages after Rad21 deletion \(mean 13.6% of control, 13 biological replicates\ \). b, Regulation of inducible gen:2589)/F 4/H/N/Rect[278.358 286.82 286.3 272.777]/Subtype/Link/Type/Annot>> endobj 59 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatImmun_184.indd:Fig. 2 | Cohesin promotes inducible gene expression. a, Immunoblot an\ alysis of RAD21 protein expression in mature macrophages after Rad21 deletion \(mean 13.6% of control, 13 biological replicate\ s\). b, Regulation of inducible ge:2590)/F 4/H/N/Rect[248.547 202.206 257.363 189.66]/Subtype/Link/Type/Annot>> endobj 60 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatImmun_184.indd: 44. Tachibana-Konwalski, K. et al. Rec8-containing cohesin maintains bivalents wit\ hout turnover during the growing phase of mouse oocytes. Genes Dev. 24, 2505 2516 \(2010\).\r:2591)/F 4/H/N/Rect[243.826 97.2059 249.031 84.6602]/Subtype/Link/Type/Annot>> endobj 61 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatImmun_184.indd:Fig. 3 | Identification of immediate cohesin target genes. a, Experimental sy\ stem for TEV-induced cleavage of RAD21-TEV. Macrophages were generated from the livers of Rad21-TEV-Myc embryos44. RAD21 p\ rotein was quantified by fluoresce:2592)/F 4/H/N/Rect[362.052 727.206 370.599 714.66]/Subtype/Link/Type/Annot>> endobj 62 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatImmun_184.indd:Fig. 3 | Identification of immediate cohesin target genes. a, Experimental s\ ystem for TEV-induced cleavage of RAD21-TEV. Macrophages were generated from the livers of Rad21-TEV-Myc embryos44. RAD21 \ protein was quantified by fluoresc:2593)/F 4/H/N/Rect[541.717 664.206 550.636 651.66]/Subtype/Link/Type/Annot>> endobj 63 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatImmun_184.indd:Fig. 3 | Identification of immediate cohesin target genes. a, Experimental \ system for TEV-induced cleavage of RAD21-TEV. Macrophages were generated from the livers of Rad21-TEV-Myc embryos44. RAD21\ protein was quantified by fluores:2594)/F 4/H/N/Rect[320.64 580.206 329.828 567.66]/Subtype/Link/Type/Annot>> endobj 64 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatImmun_184.indd: 23. Bhatt, D. M. et al. Transcript dynamics of proinflammatory genes \nrev\ ealed by sequence analysis of subcellular RNA fractions. Cell 150, \n279 290 \(2012\).\r:2595)/F 4/H/N/Rect[397.154 580.206 402.359 567.66]/Subtype/Link/Type/Annot>> endobj 65 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatImmun_184.indd: 24. Chen, X. et al. Requirement for the histone deacetylase Hdac3 for the inflam\ matory gene expression program in macrophages. Proc. Natl Acad. Sci. USA 109, E2865 E2874 \(2012\).\r:2596)/F 4/H/N/Rect[465.298 569.706 470.503 557.16]/Subtype/Link/Type/Annot>> endobj 66 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatImmun_184.indd:Fig. 3 | Identification of immediate cohesin target genes. a, Experimental\ system for TEV-induced cleavage of RAD21-TEV. Macrophages were generated from the livers of Rad21-TEV-Myc embryos44. RAD2\ 1 protein was quantified by fluore:2597)/F 4/H/N/Rect[345.901 559.206 355.089 546.66]/Subtype/Link/Type/Annot>> endobj 67 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatImmun_184.indd:Fig. 3 | Identification of immediate cohesin target genes. a, Experimenta\ l system for TEV-induced cleavage of RAD21-TEV. Macrophages were generated from the livers of Rad21-TEV-Myc embryos44. RAD\ 21 protein was quantified by fluor:2598)/F 4/H/N/Rect[380.068 548.706 388.428 536.16]/Subtype/Link/Type/Annot>> endobj 68 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatImmun_184.indd: 23. Bhatt, D. M. et al. Transcript dynamics of proinflammatory genes \nre\ vealed by sequence analysis of subcellular RNA fractions. Cell 150, \n279 290 \(2012\).\r:2599)/F 4/H/N/Rect[473.738 548.706 478.922 536.16]/Subtype/Link/Type/Annot>> endobj 69 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatImmun_184.indd: 21. Kaikkonen, M. U. et al. Remodeling of the enhancer landscape during macro\ phage activation is coupled to enhancer transcription. Mol. Cell 51, 310 325 \(2013\).\r:2605)/F 4/H/N/Rect[395.394 391.206 400.599 378.66]/Subtype/Link/Type/Annot>> endobj 70 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatImmun_184.indd: 22. Ostuni, R. et al. Latent enhancers activated by stimulation in differentiated \ cells. Cell 152, 157 171 \(2013\).\r:2606)/F 4/H/N/Rect[401.836 391.206 407.041 378.66]/Subtype/Link/Type/Annot>> endobj 71 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatImmun_184.indd: 22. Ostuni, R. et al. Latent enhancers activated by stimulation in differentiated\ cells. Cell 152, 157 171 \(2013\).\r:2607)/F 4/H/N/Rect[437.727 349.327 442.932 336.66]/Subtype/Link/Type/Annot>> endobj 72 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatImmun_184.indd: 22. Ostuni, R. et al. Latent enhancers activated by stimulation in differentiate\ d cells. Cell 152, 157 171 \(2013\).\r:2608)/F 4/H/N/Rect[406.384 328.82 411.589 314.777]/Subtype/Link/Type/Annot>> endobj 73 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatImmun_184.indd:Fig. 4 | Restricted enhancer dynamics in cohesin-deficient macrophages. Left, h\ eat map of H3K27ac ChIP-seq signals for constitutively active \(8,991\), inducible \(6,708\), and repressed \(11,146\) enhancers2\ 2. z-scores were calculated on th:2609)/F 4/H/N/Rect[542.954 328.82 547.418 314.777]/Subtype/Link/Type/Annot>> endobj 74 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatImmun_184.indd: 22. Ostuni, R. et al. Latent enhancers activated by stimulation in differentiat\ ed cells. Cell 152, 157 171 \(2013\).\r:2610)/F 4/H/N/Rect[341.404 307.206 346.609 294.66]/Subtype/Link/Type/Annot>> endobj 75 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatImmun_184.indd:Fig. 4 | Restricted enhancer dynamics in cohesin-deficient macrophages. Left, \ heat map of H3K27ac ChIP-seq signals for constitutively active \(8,991\), inducible \(6,708\), and repressed \(11,146\) enhancers\ 22. z-scores were calculated on t:2611)/F 4/H/N/Rect[335.895 296.706 340.359 284.16]/Subtype/Link/Type/Annot>> endobj 76 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatImmun_184.indd: 22. Ostuni, R. et al. Latent enhancers activated by stimulation in differentia\ ted cells. Cell 152, 157 171 \(2013\).\r:2612)/F 4/H/N/Rect[314.397 286.82 319.602 272.777]/Subtype/Link/Type/Annot>> endobj 77 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatImmun_184.indd: 23. Bhatt, D. M. et al. Transcript dynamics of proinflammatory genes \ \nrevealed by sequence analysis of subcellular RNA fractions. Cell 150, \n279 290 \(2012\).\r:2614)/F 4/H/N/Rect[415.337 170.706 420.542 158.16]/Subtype/Link/Type/Annot>> endobj 78 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatImmun_184.indd: 22. Ostuni, R. et al. Latent enhancers activated by stimulation in different\ iated cells. Cell 152, 157 171 \(2013\).\r:2615)/F 4/H/N/Rect[381.798 160.82 387.003 146.777]/Subtype/Link/Type/Annot>> endobj 79 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatImmun_184.indd: 45. Zlotnik, A., Yoshie, O. & Nomiyama, H. The chemokine and chemokine receptor su\ perfamilies and their molecular evolution. 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Fudenberg, G. et al. Formation of chromosomal domains by loop extrusion. Cell\ Rep. 15, 2038 2049 \(2016\).\r:2617)/F 4/H/N/Rect[254.614 76.2068 257.216 63.6611]/Subtype/Link/Type/Annot>> endobj 88 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatImmun_184.indd: 3. Rao, S. S. P. et al. A 3D map of the human genome at kilobase resolution revea\ ls principles of chromatin looping. Cell 159, 1665 1680 \(2014\).\r:2618)/F 4/H/N/Rect[258.453 76.2068 261.055 63.6611]/Subtype/Link/Type/Annot>> endobj 89 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatImmun_184.indd: 4. Rao, S. S. P. et al. Cohesin loss eliminates all loop domains. Cell 171,\ 305 320.e24 \(2017\).\r:2619)/F 4/H/N/Rect[262.291 76.2068 264.894 63.6611]/Subtype/Link/Type/Annot>> endobj 90 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatImmun_184.indd: 8. Merkenschlager, M. & Nora, E. P. CTCF and cohesin in genome folding \nand trans\ criptional gene regulation. Annu. Rev. Genomics Hum. Genet. 17, 17 43 \(2016\).\r:2620)/F 4/H/N/Rect[266.13 76.2068 268.732 63.6611]/Subtype/Link/Type/Annot>> endobj 91 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatImmun_184.indd: 46. Azofeifa, J. G., Allen, M. A., Lladser, M. E. & Dowell, R. D. An annotation agnos\ tic algorithm for detecting nascent RNA transcripts in GRO-Seq. \nIEEE/ACM Trans. Comput. Biol. Bioinform. 14, 1070 1081 \(\ 2017\).\r:2621)/F 4/H/N/Rect[396.047 55.2068 401.252 42.6611]/Subtype/Link/Type/Annot>> endobj 92 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatImmun_184.indd: 21. Kaikkonen, M. U. et al. Remodeling of the enhancer landscape during macroph\ age activation is coupled to enhancer transcription. Mol. Cell 51, 310 325 \(2013\).\r:2572)/F 4/H/N/Rect[486.786 286.634 490.937 276.29]/Subtype/Link/Type/Annot>> endobj 93 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatImmun_184.indd: 25. Glass, C. K. & Natoli, G. Molecular control of activation and priming in ma\ crophages. Nat. 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Hakimi, M.-A. et al. A chromatin remodelling complex that loads cohesin onto h\ uman chromosomes. Nature 418, 994 998 \(2002\).\r:2622)/F 4/H/N/Rect[228.422 212.707 233.627 200.161]/Subtype/Link/Type/Annot>> endobj 114 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatImmun_184.indd: 50. Lopez-Serra, L., Kelly, G., Patel, H., Stewart, A. & Uhlmann, F. The \nScc2 Scc\ 4 complex acts in sister chromatid cohesion and transcriptional regulation by maintaining nucleosome-free regions. Nat. Genet.\ 46, 1147 1151 \(2014\).\r:2623)/F 4/H/N/Rect[236.447 212.707 241.652 200.161]/Subtype/Link/Type/Annot>> endobj 115 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatImmun_184.indd: 46. Azofeifa, J. G., Allen, M. A., Lladser, M. E. & Dowell, R. D. An annotation agno\ stic algorithm for detecting nascent RNA transcripts in GRO-Seq. \nIEEE/ACM Trans. Comput. Biol. Bioinform. 14, 1070 1081 \ \(2017\).\r:2624)/F 4/H/N/Rect[339.406 412.821 344.611 398.778]/Subtype/Link/Type/Annot>> endobj 116 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatImmun_184.indd:Fig. 5 | Inducible enhancers with ISRE or IRF-PU.1 motifs are more likely to fail.\ a, Inducible enhancers22 \(H3K27ac log2FC "e 1.5\) with GRO-seq-mappable TSSs were classified as failed \(reduced H3K\ 27ac in Rad21"/" macrophages, ad:2625)/F 4/H/N/Rect[497.633 349.821 506.18 335.778]/Subtype/Link/Type/Annot>> endobj 117 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatImmun_184.indd:Fig. 5 | Inducible enhancers with ISRE or IRF-PU.1 motifs are more likely to fail.\ a, Inducible enhancers22 \(H3K27ac log2FC "e 1.5\) with GRO-seq-mappable TSSs were classified as failed \(reduced H3\ K27ac in Rad21"/" macrophages, a:2626)/F 4/H/N/Rect[411.364 307.821 420.478 293.778]/Subtype/Link/Type/Annot>> endobj 118 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatImmun_184.indd:Table 1 | Inducible enhancers with ISRE/IRF-PU.1 motifs are significantly more likely\ to fail than inducible enhancers with NF-B or NFAT motifs\r:2627)/F 4/H/N/Rect[482.359 276.321 486.823 262.278]/Subtype/Link/Type/Annot>> endobj 119 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatImmun_184.indd:Fig. 5 | Inducible enhancers with ISRE or IRF-PU.1 motifs are more likely to fail\ . a, Inducible enhancers22 \(H3K27ac log2FC "e 1.5\) with GRO-seq-mappable TSSs were classified as failed \(reduced H\ 3K27ac in Rad21"/" macrophages, :2628)/F 4/H/N/Rect[403.406 233.707 411.803 221.161]/Subtype/Link/Type/Annot>> endobj 120 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatImmun_184.indd: 23. Bhatt, D. M. et al. Transcript dynamics of proinflammatory genes\ \nrevealed by sequence analysis of subcellular RNA fractions. Cell 150, \n279 290 \(2012\).\r:2630)/F 4/H/N/Rect[372.515 149.707 377.72 137.161]/Subtype/Link/Type/Annot>> endobj 121 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatImmun_184.indd: 25. Glass, C. K. & Natoli, G. Molecular control of activation and priming in\ macrophages. Nat. Immunol. 17, 26 33 \(2016\).\r:2631)/F 4/H/N/Rect[380.54 149.707 385.745 137.161]/Subtype/Link/Type/Annot>> endobj 122 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatImmun_184.indd: 51. Schieber, T. A. et al. Information theory perspective on network robustness. \ Phys. Lett. A 380, 359 364 \(2016\).\r:2632)/F 4/H/N/Rect[395.207 107.707 400.412 95.1611]/Subtype/Link/Type/Annot>> endobj 123 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatImmun_184.indd: 44. Tachibana-Konwalski, K. et al. Rec8-containing cohesin maintains bivalents wi\ thout turnover during the growing phase of mouse oocytes. Genes Dev. 24, 2505 2516 \(2010\).\r:2600)/F 4/H/N/Rect[183.47 522.008 189.002 511.768]/Subtype/Link/Type/Annot>> endobj 124 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatImmun_184.indd: 23. Bhatt, D. M. et al. Transcript dynamics of proinflammatory genes \nr\ evealed by sequence analysis of subcellular RNA fractions. Cell 150, \n279 290 \(2012\).\r:2601)/F 4/H/N/Rect[369.339 511.852 374.273 499.772]/Subtype/Link/Type/Annot>> endobj 125 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatImmun_184.indd: 23. Bhatt, D. M. et al. Transcript dynamics of proinflammatory genes \n\ revealed by sequence analysis of subcellular RNA fractions. Cell 150, \n279 290 \(2012\).\r:2602)/F 4/H/N/Rect[452.579 490.508 457.513 480.268]/Subtype/Link/Type/Annot>> endobj 126 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatImmun_184.indd: 24. Chen, X. et al. 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Expression in \ Rad21"/" relative to control m:2633)/F 4/H/N/Rect[195.539 170.707 204.085 158.161]/Subtype/Link/Type/Annot>> endobj 149 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatImmun_184.indd:Fig. 6 | Rescue of inducible genes and enhancers in the absence of cohesin. a\ , Quantitative RT-PCR analysis of Stat1, Stat2 and Irf7 expression by control and Rad21"/" macrophages. Expression in\ Rad21"/" relative to control :2635)/F 4/H/N/Rect[61.5715 118.207 70.7598 105.661]/Subtype/Link/Type/Annot>> endobj 150 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatImmun_184.indd:Fig. 6 | Rescue of inducible genes and enhancers in the absence of cohesin. \ a, Quantitative RT-PCR analysis of Stat1, Stat2 and Irf7 expression by control and Rad21"/" macrophages. Expression i\ n Rad21"/" relative to control:2636)/F 4/H/N/Rect[75.2893 65.7068 83.5569 53.1611]/Subtype/Link/Type/Annot>> endobj 151 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatImmun_184.indd: 23. Bhatt, D. M. et al. Transcript dynamics of proinflammatory gen\ es \nrevealed by sequence analysis of subcellular RNA fractions. Cell 150, \n279 290 \(2012\).\r:2637)/F 4/H/N/Rect[66.5968 55.2068 71.7258 42.6611]/Subtype/Link/Type/Annot>> endobj 152 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatImmun_184.indd:Fig. 6 | Rescue of inducible genes and enhancers in the absence of cohesin. \ a, Quantitative RT-PCR analysis of Stat1, Stat2 and Irf7 expression by control and Rad21"/" macrophages. Expression \ in Rad21"/" relative to contro:2638)/F 4/H/N/Rect[322.005 538.207 331.249 525.661]/Subtype/Link/Type/Annot>> endobj 153 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatImmun_184.indd: 45. Zlotnik, A., Yoshie, O. & Nomiyama, H. The chemokine and chemokine receptor s\ uperfamilies and their molecular evolution. Genome Biol. 7, \n243 \(2006\).\r:2639)/F 4/H/N/Rect[533.798 527.707 538.928 515.161]/Subtype/Link/Type/Annot>> endobj 154 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatImmun_184.indd: 17. Seitan, V. C. et al. A role for cohesin in T-cell-receptor rearrangement a\ nd thymocyte differentiation. Nature 476, 467 471 \(2011\).\r:2640)/F 4/H/N/Rect[376.626 506.707 381.831 494.161]/Subtype/Link/Type/Annot>> endobj 155 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatImmun_184.indd: 4. Rao, S. S. P. et al. Cohesin loss eliminates all loop domains. Cell 171\ , 305 320.e24 \(2017\).\r:2641)/F 4/H/N/Rect[341.404 496.207 344.007 483.661]/Subtype/Link/Type/Annot>> endobj 156 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatImmun_184.indd: 7. Schwarzer, W. et al. Two independent modes of chromatin organization reveal\ ed by cohesin removal. Nature 551, 51 56 \(2017\).\r:2642)/F 4/H/N/Rect[345.243 496.207 347.846 483.661]/Subtype/Link/Type/Annot>> endobj 157 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatImmun_184.indd: 20. Ing-Simmons, E. et al. Spatial enhancer clustering and regulation of enhancer\ -proximal genes by cohesin. Genome Res. 25, 504 513 \(2015\).\r:2643)/F 4/H/N/Rect[349.082 496.207 354.287 483.661]/Subtype/Link/Type/Annot>> endobj 158 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatImmun_184.indd: 4. Rao, S. S. P. et al. Cohesin loss eliminates all loop domains. Cell 171\ , 305 320.e24 \(2017\).\r:2644)/F 4/H/N/Rect[380.043 254.707 382.645 242.161]/Subtype/Link/Type/Annot>> endobj 159 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatImmun_184.indd: 7. Schwarzer, W. et al. Two independent modes of chromatin organization revea\ led by cohesin removal. Nature 551, 51 56 \(2017\).\r:2645)/F 4/H/N/Rect[383.881 254.707 386.484 242.161]/Subtype/Link/Type/Annot>> endobj 160 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatImmun_184.indd: 20. Ing-Simmons, E. et al. Spatial enhancer clustering and regulation of enhance\ r-proximal genes by cohesin. Genome Res. 25, 504 513 \(2015\).\r:2646)/F 4/H/N/Rect[387.72 254.707 392.925 242.161]/Subtype/Link/Type/Annot>> endobj 161 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatImmun_184.indd: 35. Baldridge, M. T., King, K. Y., Boles, N. C., Weksberg, D. C. & Goodell, M. A.\ Quiescent haematopoietic stem cells are activated by IFN- in response to chronic infection. Nature 465, 793 797 \(2010\).\ \r:2647)/F 4/H/N/Rect[537.406 170.707 542.611 158.161]/Subtype/Link/Type/Annot>> endobj 162 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatImmun_184.indd: 42. Zhao, J. L. et al. Conversion of danger signals into cytokine signals by hema\ topoietic stem and progenitor cells for regulation of stress-induced hematopoiesis. Cell Stem Cell 14, 445 459 \(2014\).\r:2\ 648)/F 4/H/N/Rect[545.431 170.707 550.636 158.161]/Subtype/Link/Type/Annot>> endobj 163 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatImmun_184.indd: 40. Nagai, Y. et al. Toll-like receptors on hematopoietic progenitor cells stimula\ te innate immune system replenishment. Immunity 24, 801 812 \(2006\).\r:2649)/F 4/H/N/Rect[532.548 149.707 537.753 137.161]/Subtype/Link/Type/Annot>> endobj 164 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatImmun_184.indd: 42. Zhao, J. L. et al. Conversion of danger signals into cytokine signals by hem\ atopoietic stem and progenitor cells for regulation of stress-induced hematopoiesis. Cell Stem Cell 14, 445 459 \(2014\).\r:\ 2650)/F 4/H/N/Rect[538.989 149.707 544.194 137.161]/Subtype/Link/Type/Annot>> endobj 165 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatImmun_184.indd: 52. Painter, M. W., Davis, S., Hardy, R. R., Mathis, D. & Benoist, C. Transcriptom\ es of the B and T lineages compared by multiplatform microarray profiling. J. 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Leukemia-associated cohesin mutants dominantly enforce \ stem cell programs and impair human hematopoietic progenitor differentiation. Cell Stem Cell 17, 675 688 \(2015\).\r:2654)/F 4/H/N/Rect[326.125 107.707 331.33 95.1611]/Subtype/Link/Type/Annot>> endobj 169 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatImmun_184.indd: 32. Viny, A. D. et al. Dose-dependent role of the cohesin complex in normal and ma\ lignant hematopoiesis. J. Exp. Med. 212, 1819 1832 \(2015\).\r:2655)/F 4/H/N/Rect[334.149 107.707 339.354 95.1611]/Subtype/Link/Type/Annot>> endobj 170 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatImmun_184.indd: 32. Viny, A. D. et al. Dose-dependent role of the cohesin complex in normal and m\ alignant hematopoiesis. J. Exp. Med. 212, 1819 1832 \(2015\).\r:2656)/F 4/H/N/Rect[545.431 107.707 550.636 95.1611]/Subtype/Link/Type/Annot>> endobj 171 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatImmun_184.indd: 31. Mullenders, J. et al. Cohesin loss alters adult hematopoietic stem cell homeos\ tasis, leading to myeloproliferative neoplasms. J. Exp. Med. 212, 1833 1850 \(2015\).\r:2657)/F 4/H/N/Rect[446.528 76.3277 451.733 63.6611]/Subtype/Link/Type/Annot>> endobj 172 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatImmun_184.indd:Fig. 7 | Cohesin controls inflammatory gene expression in HSPCs. GSEA analysis \ of inflammatory gene expression by HSPCs after Stag2 versus control RNAi \(FDR = 2.96 10 4, data from ref. 31\). NES,\ normalized enrichment score.:2658)/F 4/H/N/Rect[499.598 65.7068 504.062 53.1611]/Subtype/Link/Type/Annot>> endobj 173 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatImmun_184.indd: 31. Mullenders, J. et al. Cohesin loss alters adult hematopoietic stem cell homeo\ stasis, leading to myeloproliferative neoplasms. J. Exp. 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