Chromosome Research

, Volume 26, Issue 1–2, pp 61–84 | Cite as

Contribution of transposable elements and distal enhancers to evolution of human-specific features of interphase chromatin architecture in embryonic stem cells

  • Gennadi V. Glinsky
Original Article


Transposable elements have made major evolutionary impacts on creation of primate-specific and human-specific genomic regulatory loci and species-specific genomic regulatory networks (GRNs). Molecular and genetic definitions of human-specific changes to GRNs contributing to development of unique to human phenotypes remain a highly significant challenge. Genome-wide proximity placement analysis of diverse families of human-specific genomic regulatory loci (HSGRL) identified topologically associating domains (TADs) that are significantly enriched for HSGRL and designated rapidly evolving in human TADs. Here, the analysis of HSGRL, hESC-enriched enhancers, super-enhancers (SEs), and specific sub-TAD structures termed super-enhancer domains (SEDs) has been performed. In the hESC genome, 331 of 504 (66%) of SED-harboring TADs contain HSGRL and 68% of SEDs co-localize with HSGRL, suggesting that emergence of HSGRL may have rewired SED-associated GRNs within specific TADs by inserting novel and/or erasing existing non-coding regulatory sequences. Consequently, markedly distinct features of the principal regulatory structures of interphase chromatin evolved in the hESC genome compared to mouse: the SED quantity is 3-fold higher and the median SED size is significantly larger. Concomitantly, the overall TAD quantity is increased by 42% while the median TAD size is significantly decreased (p = 9.11E-37) in the hESC genome. Present analyses illustrate a putative global role for transposable elements and HSGRL in shaping the human-specific features of the interphase chromatin organization and functions, which are facilitated by accelerated creation of novel transcription factor binding sites and new enhancers driven by targeted placement of HSGRL at defined genomic coordinates. A trend toward the convergence of TAD and SED architectures of interphase chromatin in the hESC genome may reflect changes of 3D-folding patterns of linear chromatin fibers designed to enhance both regulatory complexity and functional precision of GRNs by creating predominantly a single gene (or a set of functionally linked genes) per regulatory domain structures. Collectively, present analyses reveal critical evolutionary contributions of transposable elements and distal enhancers to creation of thousands primate- and human-specific elements of a chromatin folding code, which defines the 3D context of interphase chromatin both restricting and facilitating biological functions of GRNs.


Topologically associating domains Super-enhancers Super-enhancer domains Human-specific genomic regulatory sequences Chromatin loops Human ESC Pluripotent state regulators NANOG POU5F1 (OCT4) CTCF Methyl-cytosine deamination Recombination Alu elements LTR7 RNAs L1 retrotransposition LINE LTR LTR7/HERVH LTR5_HS/HERVK Evolution of Modern Humans 





CCCTC-binding factor


DNase hypersensitivity sites


fixed human-specific regulatory regions


genomic regulatory networks


human-accelerated regions


human-specific conserved deletions


human embryonic stem cells


human-specific genomic regulatory loci


human-specific NANOG-binding sites


human-specific transcription factor-binding sites


lamina-associated domain


long interspersed nuclear element


long non-coding RNA


long terminal repeat


methylation-associated DNA editing




mouse embryonic stem cells


Nanog homeobox




POU class 5 homeobox 1


topologically associating domains


transposable elements


transcription factor




super-enhancer domains



This work was made possible by the open public access policies of major grant funding agencies and international genomic databases and the willingness of many investigators worldwide to share their primary research data. I would like to thank my colleagues for their valuable critical contributions during the informal review and formal peer review process of this work.

Author contributions

This is a single author contribution. All elements of this work, including the conception of ideas, formulation, and development of concepts, execution of experiments, analysis of data, and writing of the paper, were performed by the author.

Supplementary material

10577_2018_9571_MOESM1_ESM.pdf (79 kb)
ESM 1 (PDF 78.7 kb)
10577_2018_9571_MOESM2_ESM.pdf (1.4 mb)
ESM 2 (PDF 1.40 mb)
10577_2018_9571_MOESM3_ESM.pdf (54 kb)
ESM 3 (PDF 54.3 kb)
10577_2018_9571_MOESM4_ESM.pdf (260 kb)
ESM 4 (PDF 260 kb)
10577_2018_9571_MOESM5_ESM.docx (17 kb)
ESM 5 (DOCX 17.3 kb)


  1. Abecasis GR, Auton A, Brooks LD, DePristo MA, Durbin RM, Handsaker RE, Kang HM, Marth GT, McVean GA, 1000 Genomes Project Consortium (2012) An integrated map of genetic variation from 1,092 human genomes. Nature 491:56–65CrossRefPubMedGoogle Scholar
  2. Bennett EA, Keller H, Mills RE, Schmidt S, Moran JV, Weichenrieder O, Devine SE (2008) Active Alu retrotransposons in the human genome. Genome Res 18(12):1875–1883. CrossRefPubMedPubMedCentralGoogle Scholar
  3. Bird C, Stranger B, Liu M, Thomas D, Ingle C, Beazley C, Miller W, Hurles M, Dermitzakis E (2007) Fast-evolving noncoding sequences in the human genome. Genome Biol 8(6):R118. CrossRefPubMedPubMedCentralGoogle Scholar
  4. Capra JA, Erwin GD, McKinsey G, Rubenstein JL, Pollard KS (2013) Many human accelerated regions are developmental enhancers. Philos Trans R Soc Lond Ser B Biol Sci 368(1632):20130025. CrossRefGoogle Scholar
  5. Chimpanzee sequencing and analysis consortium (2005) Initial sequence of the chimpanzee genome and comparison with the human genome. Nature 437(7055):69–87. CrossRefGoogle Scholar
  6. Cotney J, Leng J, Yin J, Reilly SK, DeMare LE, Emera D, Ayoub AE, Rakic P, Noonan JP (2013) The evolution of lineage-specific regulatory activities in the human embryonic limb. Cell 154(1):185–196. CrossRefPubMedPubMedCentralGoogle Scholar
  7. Dixon JR, Selvaraj S, Yue F, Kim A, Li Y, Shen Y, Hu M, Liu JS, Ren B (2012) Topological domains in mammalian genomes identified by analysis of chromatin interactions. Nature 485(7398):376–380. CrossRefPubMedPubMedCentralGoogle Scholar
  8. Dong X, Wang X, Zhang F, Tian W (2016) Genome-wide identification of regulatory sequences undergoing accelerated evolution in the human genome. Mol Biol Evol 33(10):2565–2575. CrossRefPubMedPubMedCentralGoogle Scholar
  9. Dowen JM, Fan ZP, Hnisz D, Ren G, Abraham BJ, Zhang LN, Weintraub AS, Schuijers J, Lee TI, Zhao K, Young RA (2014) Control of cell identity genes occurs in insulated neighborhoods in mammalian chromosomes. Cell 159(2):374–387. CrossRefPubMedPubMedCentralGoogle Scholar
  10. Duque T, Samee MA, Kazemian M, Pham HN, Brodsky MH, Sinha S (2014) Simulations of enhancer evolution provide mechanistic insights into gene regulation. Mol Biol Evol 31(1):184–200. CrossRefPubMedGoogle Scholar
  11. Ernst J, Kellis M (2013) Interplay between chromatin state, regulator binding, and regulatory motifs in six human cell types. Genome Res 23:142–1154CrossRefGoogle Scholar
  12. Fu Q, Li H, Moorjani P, Jay F, Slepchenko SM, Bondarev AA, Johnson PL, Aximu-Petri A, Prüfer K, de Filippo C, Meyer M, Zwyns N, Salazar-García DC, Kuzmin YV, Keates SG, Kosintsev PA, Razhev DI, Richards MP, Peristov NV, Lachmann M, Douka K, Higham TF, Slatkin M, Hublin JJ, Reich D, Kelso J, Viola TB, Pääbo S (2014) Genome sequence of a 45,000-year-old modern human from western Siberia. Nature 514(7523):445–449. CrossRefPubMedPubMedCentralGoogle Scholar
  13. Gittelman RM, Hun E, Ay F, Madeoy J, Pennacchio L, Noble WS, Hawkins RD, Akey JM (2015) Comprehensive identification and analysis of human accelerated regulatory DNA. Genome Res 25(9):1245–1255. CrossRefPubMedPubMedCentralGoogle Scholar
  14. Glinsky GV (2015a) Transposable elements and DNA methylation create in embryonic stem cells human-specific regulatory sequences associated with distal enhancers and non-coding RNAs. Genome Biol Evol 7(6):1432–1454. CrossRefPubMedPubMedCentralGoogle Scholar
  15. Glinsky GV (2015b) Viruses, stemness, embryogenesis, and cancer: a miracle leap toward molecular definition of novel oncotargets for therapy resistant malignant tumors? Oncoscience 2(9):751–754. PubMedPubMedCentralGoogle Scholar
  16. Glinsky GV (2016a) Mechanistically distinct pathways of divergent regulatory DNA creation contribute to evolution of human-specific genomic regulatory networks driving phenotypic divergence of Homo Sapiens. Genome Biol Evol 8(9):2774–2788. CrossRefPubMedPubMedCentralGoogle Scholar
  17. Glinsky GV (2016b) Activation of endogenous human stem cell-associated retroviruses (SCARs) and therapy-resistant phenotypes of malignant tumors. Cancer Lett 376(2):347–359. CrossRefPubMedGoogle Scholar
  18. Glinsky GV (2016c) Single cell genomics reveals activation signatures of endogenous SCAR's networks in aneuploid human embryos and clinically intractable malignant tumors. Cancer Lett 381(1):176–193. CrossRefPubMedGoogle Scholar
  19. Glinsky GV (2017) Human-specific features of pluripotency regulatory networks link NANOG with fetal and adult brain development.; doi:
  20. Gorkin DU, Leung D, Ren B (2014) The 3D genome in transcriptional regulation and pluripotency. Cell Stem Cell 14(6):762–775. CrossRefPubMedPubMedCentralGoogle Scholar
  21. Green RE, Krause J, Briggs AW, Maricic T, Stenzel U, Kircher M, Patterson N, Li H, Zhai W, Fritz MHY, Hansen NF, Durand EY, Malaspinas AS, Jensen JD, Marques-Bonet T, Alkan C, Prufer K, Meyer M, Burbano HA, Good JM, Schultz R, Aximu-Petri A, Butthof A, Hober B, Hoffner B, Siegemund M, Weihmann A, Nusbaum C, Lander ES, Russ C, Novod N, Affourtit J, Egholm M, Verna C, Rudan P, Brajkovic D, Kucan Z, Gusic I, Doronichev VB, Golovanova LV, Lalueza-Fox C, de la Rasilla M, Fortea J, Rosas A, Schmitz RW, Johnson PLF, Eichler EE, Falush D, Birney E, Mullikin JC, Slatkin M, Nielsen R, Kelso J, Lachmann M, Reich D, Paabo S (2010) A draft sequence of the Neanderthal genome. Science 328(5979):710–722. CrossRefPubMedPubMedCentralGoogle Scholar
  22. Guelen L, Pagie L, Brasset E, Meuleman W, Faza MB, Talhout W, Eussen BH, de Klein A, Wessels L, de Laat W, van Steensel B (2008) Domain organization of human chromosomes revealed by mapping of nuclear lamina interactions. Nature 453(7197):948–951. CrossRefPubMedGoogle Scholar
  23. Guttman M, Donaghey J, Carey BW, Garber M, Grenier JK, Munson G, Young G, Lucas AB, Ach R, Bruhn L, Yang X, Amit I, Meissner A, Regev A, Rinn JL, Root DE, Lander ES (2011) lincRNAs act in the circuitry controlling pluripotency and differentiation. Nature 477(7364):295–300. CrossRefPubMedPubMedCentralGoogle Scholar
  24. He X, Duque TS, Sinha S (2012) Evolutionary origins of transcription factor binding site clusters. Mol Biol Evol 29(3):1059–1070. CrossRefPubMedGoogle Scholar
  25. Hnisz D, Abraham BJ, Lee TI, Lau A, Saint-André V, Sigova AA, Hoke HA, Young RA (2013) Super-enhancers in the control of cell identity and disease. Cell 155(4):934–947. CrossRefPubMedGoogle Scholar
  26. Hou C, Li L, Qin ZS, Corces VG (2012) Gene density, transcription, and insulators contribute to the partition of the drosophila genome into physical domains. Mol Cell 48(3):471–484. CrossRefPubMedPubMedCentralGoogle Scholar
  27. Huda A, Mariño-Ramírez L, Landsman D, Jordan IK (2009) Repetitive DNA elements, nucleosome binding and human gene expression. Gene 436(1-2):12–22. CrossRefPubMedPubMedCentralGoogle Scholar
  28. Kent WJ (2002) BLAT - the BLAST-like alignment tool. Genome Res 12(4):656–664. CrossRefPubMedPubMedCentralGoogle Scholar
  29. King MC, Wilson AC (1975) Evolution at two levels in humans and chimpanzees. Science 188(4184):107–116. CrossRefPubMedGoogle Scholar
  30. Konopka G, Friedrich T, Davis-Turak J, Winden K, Oldham MC, Gao F, Chen L, Wang GZ, Luo R, Preuss TM, Geschwind DH (2012) Human-specific transcriptional networks in the brain. Neuron 75(4):601–617. CrossRefPubMedPubMedCentralGoogle Scholar
  31. Kunarso G, Chia NY, Jeyakani J, Hwang C, Lu X, Chan YS, Ng HH, Bourque G (2010) Transposable elements have rewired the core regulatory network of human embryonic stem cells. Nat Genet 42:631–634CrossRefPubMedGoogle Scholar
  32. Lander ES, Linton LM, Birren B, Nusbaum C, Zody MC, Baldwin J, Devon K, Dewar K, Doyle M, FitzHugh W, Funke R, Gage D, Harris K, Heaford A, Howland J, Kann L, Lehoczky J, LeVine R, McEwan P, McKernan K, Meldrim J, Mesirov JP, Miranda C, Morris W, Naylor J, Raymond C, Rosetti M, Santos R, Sheridan A, Sougnez C, Stange-Thomann Y, Stojanovic N, Subramanian A, Wyman D, Rogers J, Sulston J, Ainscough R, Beck S, Bentley D, Burton J, Clee C, Carter N, Coulson A, Deadman R, Deloukas P, Dunham A, Dunham I, Durbin R, French L, Grafham D, Gregory S, Hubbard T, Humphray S, Hunt A, Jones M, Lloyd C, McMurray A, Matthews L, Mercer S, Milne S, Mullikin JC, Mungall A, Plumb R, Ross M, Shownkeen R, Sims S, Waterston RH, Wilson RK, Hillier LW, McPherson JD, Marra MA, Mardis ER, Fulton LA, Chinwalla AT, Pepin KH, Gish WR, Chissoe SL, Wendl MC, Delehaunty KD, Miner TL, Delehaunty A, Kramer JB, Cook LL, Fulton RS, Johnson DL, Minx PJ, Clifton SW, Hawkins T, Branscomb E, Predki P, Richardson P, Wenning S, Slezak T, Doggett N, Cheng JF, Olsen A, Lucas S, Elkin C, Uberbacher E, Frazier M, Gibbs RA, Muzny DM, Scherer SE, Bouck JB, Sodergren EJ, Worley KC, Rives CM, Gorrell JH, Metzker ML, Naylor SL, Kucherlapati RS, Nelson DL, Weinstock GM, Sakaki Y, Fujiyama A, Hattori M, Yada T, Toyoda A, Itoh T, Kawagoe C, Watanabe H, Totoki Y, Taylor T, Weissenbach J, Heilig R, Saurin W, Artiguenave F, Brottier P, Bruls T, Pelletier E, Robert C, Wincker P, Smith DR, Doucette-Stamm L, Rubenfield M, Weinstock K, Lee HM, Dubois J, Rosenthal A, Platzer M, Nyakatura G, Taudien S, Rump A, Yang H, Yu J, Wang J, Huang G, Gu J, Hood L, Rowen L, Madan A, Qin S, Davis RW, Federspiel NA, Abola AP, Proctor MJ, Myers RM, Schmutz J, Dickson M, Grimwood J, Cox DR, Olson MV, Kaul R, Raymond C, Shimizu N, Kawasaki K, Minoshima S, Evans GA, Athanasiou M, Schultz R, Roe BA, Chen F, Pan H, Ramser J, Lehrach H, Reinhardt R, McCombie WR, de la Bastide M, Dedhia N, Blöcker H, Hornischer K, Nordsiek G, Agarwala R, Aravind L, Bailey JA, Bateman A, Batzoglou S, Birney E, Bork P, Brown DG, Burge CB, Cerutti L, Chen HC, Church D, Clamp M, Copley RR, Doerks T, Eddy SR, Eichler EE, Furey TS, Galagan J, Gilbert JG, Harmon C, Hayashizaki Y, Haussler D, Hermjakob H, Hokamp K, Jang W, Johnson LS, Jones TA, Kasif S, Kaspryzk A, Kennedy S, Kent WJ, Kitts P, Koonin EV, Korf I, Kulp D, Lancet D, Lowe TM, McLysaght A, Mikkelsen T, Moran JV, Mulder N, Pollara VJ, Ponting CP, Schuler G, Schultz J, Slater G, Smit AF, Stupka E, Szustakowki J, Thierry-Mieg D, Thierry-Mieg J, Wagner L, Wallis J, Wheeler R, Williams A, Wolf YI, Wolfe KH, Yang SP, Yeh RF, Collins F, Guyer MS, Peterson J, Felsenfeld A, Wetterstrand KA, Patrinos A, Morgan MJ, de Jong P, Catanese JJ, Osoegawa K, Shizuya H, Choi S, Chen YJ, Szustakowki J, International Human Genome Sequencing Consortium (2001) Initial sequencing and analysis of the human genome. Nature 409(6822):860–921. CrossRefPubMedGoogle Scholar
  33. Lee W, Mun S, Kang K, Hennighausen L, Han K (2015) Genome-wide target site triplication of Alu elements in the human genome. Gene 561(2):283–291. CrossRefPubMedGoogle Scholar
  34. Li G, Ruan X, Auerbach RK et al (2012) Extensive promoter-centered chromatin interactions provide a topological basis for transcription regulation. Cell 148(1-2):84–98. CrossRefPubMedPubMedCentralGoogle Scholar
  35. Li Y, Huang W, Niu L, Umbach DM, Covo S, Li L (2013) Characterization of constitutive CTCF/cohesin loci: a possible role in establishing topological domains in mammalian genomes. BMC Genomics 14(1):553. CrossRefPubMedPubMedCentralGoogle Scholar
  36. Lister R, Pelizzola M, Dowen RH, Hawkins RD, Hon G, Tonti-Filippini J, Nery JR, Lee L, Ye Z, Ngo QM, Edsall L, Antosiewicz-Bourget J, Stewart R, Ruotti V, Millar AH, Thomson JA, Ren B, Ecker JR (2009) Human DNA methylomes at base resolution show widespread epigenomic differences. Nature 462(7271):315–322. CrossRefPubMedPubMedCentralGoogle Scholar
  37. Lister R, Mukamel EA, Nery JR, Urich M, Puddifoot CA, Johnson ND, Lucero J, Huang Y, Dwork AJ, Schultz MD, Yu M, Tonti-Filippini J, Heyn H, Hu S, Wu JC, Rao A, Esteller M, He C, Haghighi FG, Sejnowski TJ, Behrens MM, Ecker JR (2013) Global epigenomic reconfiguration during mammalian brain development. Science 341(6146):1237905. CrossRefPubMedPubMedCentralGoogle Scholar
  38. Marnetto D, Molineris I, Grassi E, Provero P (2014) Genome-wide identification and characterization of fixed human-specific regulatory regions. Am J Hum Genet 95(1):39–48. CrossRefPubMedPubMedCentralGoogle Scholar
  39. McLean CY, Reno PL, Pollen AA, Bassan AI, Capellini TD, Guenther C, Indjeian VB, Lim X, Menke DB, Schaar BT, Wenger AM, Bejerano G, Kingsley DM (2011) Human-specific loss of regulatory DNA and the evolution of human-specific traits. Nature 471(7337):216–219. CrossRefPubMedPubMedCentralGoogle Scholar
  40. Meyer M, Kircher M, Gansauge MT, Li H, Racimo F, Mallick S, Schraiber JG, Jay F, Prufer K, de Filippo C, Sudmant PH, Alkan C, Fu Q, Do R, Rohland N, Tandon A, Siebauer M, Green RE, Bryc K, Briggs AW, Stenzel U, Dabney J, Shendure J, Kitzman J, Hammer MF, Shunkov MV, Derevianko AP, Patterson N, Andres AM, Eichler EE, Slatkin M, Reich D, Kelso J, Paabo S (2012) A high-coverage genome sequence from an archaic Denisovan individual. Science 338(6104):222–226. CrossRefPubMedPubMedCentralGoogle Scholar
  41. Meyer LR, Zweig AS, Hinrichs AS, Karolchik D, Kuhn RM, Wong M, Sloan CA, Rosenbloom KR, Roe G, Rhead B, Raney BJ, Pohl A, Malladi VS, Li CH, Lee BT, Learned K, Kirkup V, Hsu F, Heitner S, Harte RA, Haeussler M, Guruvadoo L, Goldman M, Giardine BM, Fujita PA, Dreszer TR, Diekhans M, Cline MS, Clawson H, Barber GP, Haussler D, Kent WJ (2013) The UCSC genome browser database: extensions and updates (2013). Nucleic Acids Res 41(Database issue):D64–D69. PubMedGoogle Scholar
  42. Morales ME, White TB, Streva VA, DeFreece CB, Hedges DJ, Deininger PL (2015) The contribution of Alu elements to mutagenic DNA double-strand break repair. PLoS Genet 11(3):e1005016. CrossRefPubMedPubMedCentralGoogle Scholar
  43. Ng HH, Surani MA (2011) The transcriptional and signaling networks of pluripotency. Nat Cell Biol 13(5):490–496. CrossRefPubMedGoogle Scholar
  44. Nora EP, Lajoie BR, Schulz EG, Giorgetti L, Okamoto I, Servant N, Piolot T, van Berkum NL, Meisig J, Sedat J, Gribnau J, Barillot E, Blüthgen N, Dekker J, Heard E (2012) Spatial partitioning of the regulatory landscape of the X-inactivation centre. Nature 485(7398):381–385. CrossRefPubMedPubMedCentralGoogle Scholar
  45. Peric-Hupkes D, Meuleman W, Pagie L, Bruggeman SW, Solovei I, Brugman W, Gräf S, Flicek P, Kerkhoven RM, van Lohuizen M, Reinders M, Wessels L, van Steensel B (2010) Molecular maps of the reorganization of genome-nuclear lamina interactions during differentiation. Mol Cell 38(4):603–613. CrossRefPubMedGoogle Scholar
  46. Pollard KS, Salama SR, Lambert N, Lambot MA, Coppens S, Pedersen JS, Katzman S, King B, Onodera C, Siepel A, Kern AD, Dehay C, Igel H, Ares M, Vanderhaeghen P, Haussler D (2006) An RNA gene expressed during cortical development evolved rapidly in humans. Nature 443(7108):167–172. CrossRefPubMedGoogle Scholar
  47. Prabhakar S, Noonan JP, Paabo S, Rubin EM (2006) Accelerated evolution of conserved noncoding sequences in humans. Science 314(5800):786. CrossRefPubMedGoogle Scholar
  48. Prabhakar S, Visel A, Akiyama JA, Shoukry M, Lewis KD, Holt A, Plajzer-Frick I, Morrison H, FitzPatrick DR, Afzal V, Pennacchio LA, Rubin EM, Noonan JP (2008) Human specific gain of function in a developmental enhancer. Science 321(5894):1346–1350. CrossRefPubMedPubMedCentralGoogle Scholar
  49. Prüfer K, Munch K, Hellmann I, Akagi K, Miller JR, Walenz B, Koren S, Sutton G, Kodira C, Winer R, Knight JR, Mullikin JC, Meader SJ, Ponting CP, Lunter G, Higashino S, Hobolth A, Dutheil J, Karakoç E, Alkan C, Sajjadian S, Catacchio CR, Ventura M, Marques-Bonet T, Eichler EE, André C, Atencia R, Mugisha L, Junhold J, Patterson N, Siebauer M, Good JM, Fischer A, Ptak SE, Lachmann M, Symer DE, Mailund T, Schierup MH, Andrés AM, Kelso J, Pääbo S (2012) The bonobo genome compared with the chimpanzee and human genomes. Nature 486(7404):527–531. CrossRefPubMedPubMedCentralGoogle Scholar
  50. Prüfer K, Racimo F, Patterson N, Jay F, Sankararaman S, Sawyer S, Heinze A, Renaud G, Sudmant PH, de Filippo C, Li H, Mallick S, Dannemann M, Fu Q, Kircher M, Kuhlwilm M, Lachmann M, Meyer M, Ongyerth M, Siebauer M, Theunert C, Tandon A, Moorjani P, Pickrell J, Mullikin JC, Vohr SH, Green RE, Hellmann I, Johnson PL, Blanche H, Cann H, Kitzman JO, Shendure J, Eichler EE, Lein ES, Bakken TE, Golovanova LV, Doronichev VB, Shunkov MV, Derevianko AP, Viola B, Slatkin M, Reich D, Kelso J, Pääbo S (2014) The complete genome sequence of a Neanderthal from the Altai Mountains. Nature 505(7481):43–49. CrossRefPubMedGoogle Scholar
  51. Rao SS, Huntley MH, Durand NC, Stamenova EK, Bochkov ID, Robinson JT, Sanborn AL, Machol I, Omer AD, Lander ES, Aiden EL (2014) A 3D map of the human genome at kilobase resolution reveals principles of chromatin looping. Cell 159(7):1665–1680. CrossRefPubMedPubMedCentralGoogle Scholar
  52. Reich D, Green RE, Kircher M, Krause J, Patterson N, Durand EY, Viola B, Briggs AW, Stenzel U, Johnson PL, Maricic T, Good JM, Marques-Bonet T, Alkan C, Fu Q, Mallick S, Li H, Meyer M, Eichler EE, Stoneking M, Richards M, Talamo S, Shunkov MV, Derevianko AP, Hublin JJ, Kelso J, Slatkin M, Pääbo S (2010) Genetic history of an archaic hominin group from Denisova cave in Siberia. Nature 468(7327):1053–1060. CrossRefPubMedPubMedCentralGoogle Scholar
  53. Rosenbloom KR, Sloan CA, Malladi VS, Dreszer TR, Learned K, Kirkup VM, Wong MC, Maddren M, Fang R, Heitner SG, Lee BT, Barber GP, Harte RA, Diekhans M, Long JC, Wilder SP, Zweig AS, Karolchik D, Kuhn RM, Haussler D, Kent WJ (2013) ENCODE data in the UCSC genome browser: year 5 update. Nucleic Acids Res 41(Database issue):D56–D63. PubMedGoogle Scholar
  54. Schmidt D, Schwalie PC, Wilson MD, Ballester B, Gonçalves A, Kutter C, Brown GD, Marshall A, Flicek P, Odom DT (2012) Waves of retrotransposon expansion remodel genome organization and CTCF binding in multiple mammalian lineages. Cell 148(1-2):335–348. CrossRefPubMedPubMedCentralGoogle Scholar
  55. Schwartz S, Kent WJ, Smit A, Zhang Z, Baertsch R, Hardison RC, Haussler D, Miller W (2003) Human-mouse alignments with BLASTZ. Genome Res 13(1):103–107. CrossRefPubMedPubMedCentralGoogle Scholar
  56. Seitan VC, Faure AJ, Zhan Y, McCord RP, Lajoie BR, Ing-Simmons E, Lenhard B, Giorgetti L, Heard E, Fisher AG, Flicek P, Dekker J, Merkenschlager M (2013) Cohesin-based chromatin interactions enable regulated gene expression within preexisting architectural compartments. Genome Res 23(12):2066–2077. CrossRefPubMedPubMedCentralGoogle Scholar
  57. Sexton T, Yaffe E, Kenigsberg E, Bantignies F, Leblanc B, Hoichman M, Parrinello H, Tanay A, Cavalli G (2012) Three-dimensional folding and functional organization principles of the drosophila genome. Cell 148(3):458–472. CrossRefPubMedGoogle Scholar
  58. Shulha HP, Crisci JL, Reshetov D, Tushir JS, Cheung I, Bharadwaj R, Chou HJ, Houston IB, Peter CJ, Mitchell AC, Yao WD, Myers RH, Chen JF, Preuss TM, Rogaev EI, Jensen JD, Weng Z, Akbarian S (2012) Human-specific histone methylation signatures at transcription start sites in prefrontal neurons. PLoS Biol 10(11):e1001427. CrossRefPubMedPubMedCentralGoogle Scholar
  59. Sofueva S, Yaffe E, Chan WC, Georgopoulou D, Vietri Rudan M, Mira-Bontenbal H, Pollard SM, Schroth GP, Tanay A, Hadjur S (2013) Cohesin-mediated interactions organize chromosomal domain architecture. The. EMBO J 32(24):3119–3129. CrossRefPubMedPubMedCentralGoogle Scholar
  60. Tark-Dame M, Jerabek H, Manders EM, Heermann DW, Driel R (2014) Depletion of the chromatin looping proteins CTCF and cohesin causes chromatin compaction: insight into chromatin folding by polymer modelling. PLoS Comput Biol 10(10):e1003877. CrossRefPubMedPubMedCentralGoogle Scholar
  61. Tavazoie S, Hughes JD, Campbell MJ, Cho RJ, Church GM (1999) Systematic determination of genetic network architecture. Nat Genet 22(3):281–285. CrossRefPubMedGoogle Scholar
  62. Tay SK, Blythe J, Lipovich L (2009) Global discovery of primate-specific genes in the human genome. Proc Natl Acad Sci U S A 106(29):12019–12024. CrossRefPubMedPubMedCentralGoogle Scholar
  63. The International Hapmap Consortium (2007) A second generation human haplotype map of over 3.1 million SNPs. Nature 449:851–861CrossRefPubMedCentralGoogle Scholar
  64. Villar D, Berthelot C, Aldridge S, Rayner TF, Lukk M, Pignatelli M, Park TJ, Deaville R, Erichsen JT, Jasinska AJ, Turner JM, Bertelsen MF, Murchison EP, Flicek P, Odom DT (2015) Enhancer evolution across 20 mammalian species. Cell 160(3):554–566. CrossRefPubMedPubMedCentralGoogle Scholar
  65. Wagner GP, Altenberg L (1996) Perspective: complex adaptations and the evolution of evolvability. Evolution 50(3):967–976. CrossRefPubMedGoogle Scholar
  66. Wang J, Zhuang J, Iyer S, Lin X, Whitfield TW, Greven MC, Pierce BG, Dong X, Kundaje A, Cheng Y, Rando OJ, Birney E, Myers RM, Noble WS, Snyder M, Weng Z (2012) Sequence features and chromatin structure around the genomic regions bound by 119 human transcription factors. Genome Res 22(9):1798–1812. CrossRefPubMedPubMedCentralGoogle Scholar
  67. Weinberger L, Ayyash M, Novershtern N, Hanna JH (2016) Dynamic stem cell states: naive to primed pluripotency in rodents and humans. Nat Rev Mol Cell Biol 17(3):155–169. CrossRefPubMedGoogle Scholar
  68. Whyte WA, Orlando DA, Hnisz D, Abraham BJ, Lin CY, Kagey MH, Rahl PB, Lee TI, Young RA (2013) Master transcription factors and mediator establish super-enhancers at key cell identity genes. Cell 153(2):307–319. CrossRefPubMedPubMedCentralGoogle Scholar
  69. Xie W, Schultz MD, Lister R, Hou Z, Rajagopal N, Ray P, Whitaker JW, Tian S, Hawkins RD, Leung D, Yang H, Wang T, Lee AY, Swanson SA, Zhang J, Zhu Y, Kim A, Nery JR, Urich MA, Kuan S, Yen CA, Klugman S, Yu P, Suknuntha K, Propson NE, Chen H, Edsall LE, Wagner U, Li Y, Ye Z, Kulkarni A, Xuan Z, Chung WY, Chi NC, Antosiewicz-Bourget JE, Slukvin I, Stewart R, Zhang MQ, Wang W, Thomson JA, Ecker JR, Ren B (2013) Epigenomic analysis of multilineage differentiation of human embryonic stem cells. Cell 153(5):1134–1148. CrossRefPubMedPubMedCentralGoogle Scholar
  70. Young RA (2011) Control of the embryonic stem cell state. Cell 144(6):940–954. CrossRefPubMedPubMedCentralGoogle Scholar
  71. Zuin J, Dixon JR, van der Reijden MI, Ye Z, Kolovos P, Brouwer RW, van de Corput MP, van de Werken HJ, Knoch TA, van IJcken WF, Grosveld FG, Ren B, Wendt KS (2014) Cohesin and CTCF differentially affect chromatin architecture and gene expression in human cells. Proc Natl Acad Sci USA 111:996–1001CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media B.V., part of Springer Nature 2018
corrected publication February/2018

Authors and Affiliations

  1. 1.Institute of Engineering in MedicineUniversity of California, San DiegoLa JollaUSA

Personalised recommendations