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Cited by 94Chromosomal and Genetic VariationsGenomics and Chromatin DynamicsReproductive System and Pregnancy

Regulation of human trophoblast gene expression by endogenous retroviruses

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Frost, Jennifer M., Amante, Samuele M., Okae, Hiroaki, Jones, Eleri M., Ashley, Brogan, Lewis, Rohan M., Cleal, Jane K., Caley, Matthew P. +3 more·2023·Nature Structural & Molecular Biology
DOI 10.1038/s41594-023-00960-6PMC PMC10113160

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Abstract

The placenta is a fast-evolving organ with large morphological and histological differences across eutherians, but the genetic changes driving placental evolution have not been fully elucidated. Transposable elements, through their capacity to quickly generate genetic variation and affect host gene regulation, may have helped to define species-specific trophoblast gene expression programs. Here we assess the contribution of transposable elements to human trophoblast gene expression as enhancers or promoters. Using epigenomic data from primary human trophoblast and trophoblast stem-cell lines, we identified multiple endogenous retrovirus families with regulatory potential that lie close to genes with preferential expression in trophoblast. These largely primate-specific elements are associated with inter-species gene expression differences and are bound by transcription factors with key roles in placental development. Using genetic editing, we demonstrate that several elements act as transcriptional enhancers of important placental genes, such as CSF1R and PSG5 . We also identify an LTR10A element that regulates ENG expression, affecting secretion of soluble endoglin, with potential implications for preeclampsia. Our data show that transposons have made important contributions to human trophoblast gene regulation, and suggest that their activity may affect pregnancy outcomes.

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  1. [1]Turco MY Moffett A Development of the human placenta Development 2019 146 dev163428 10.1242/dev.163428 31776138 · DOI
  2. [3]McGinnis R Variants in the fetal genome near FLT1 are associated with risk of preeclampsia Nat. Genet. 2017 49 1255 1260 10.1038/ng.3895 28628106 · DOI
  3. [4]Carter AM Enders AC Comparative aspects of trophoblast development and placentation Reprod. Biol. Endocrinol. 2004 2 46 10.1186/1477-7827-2-46 15236656 PMC455692 · DOI
  4. [5]Carter AM Unique aspects of human placentation Int. J. Mol. Sci. 2021 22 8099 10.3390/ijms22158099 34360862 PMC8347521 · DOI
  5. [6]Chuong EB Tong W Hoekstra HE Maternal-fetal conflict: rapidly evolving proteins in the rodent placenta Mol. Biol. Evol. 2010 27 1221 1225 10.1093/molbev/msq034 20123797 PMC4031627 · DOI
  6. [7]Imakawa K Nakagawa S Miyazawa T Baton pass hypothesis: successive incorporation of unconserved endogenous retroviral genes for placentation during mammalian evolution Genes Cells 2015 20 771 788 10.1111/gtc.12278 26442811 · DOI
  7. [8]Lavialle C Paleovirology of ‘syncytins’, retroviral env genes exapted for a role in placentation Philos. Trans. R. Soc. Lond. B Biol. Sci. 2013 368 20120507 10.1098/rstb.2012.0507 23938756 PMC3758191 · DOI · Paper page
  8. [9]Fuentes DR Swigut T Wysocka J Systematic perturbation of retroviral LTRs reveals widespread long-range effects on human gene regulation eLife 2018 7 e35989 10.7554/eLife.35989 30070637 PMC6158008 · DOI
  9. [10]Pontis J Hominoid-Specific transposable elements and KZFPs facilitate human embryonic genome activation and control transcription in naive human ESCs Cell Stem Cell 2019 24 724 735 10.1016/j.stem.2019.03.012 31006620 PMC6509360 · DOI
  10. [11]Pontis J Primate-specific transposable elements shape transcriptional networks during human development Nat. Commun. 2022 13 7178 10.1038/s41467-022-34800-w 36418324 PMC9684439 · DOI
  11. [12]Chuong EB Elde NC Feschotte C Regulatory evolution of innate immunity through co-option of endogenous retroviruses Science 2016 351 1083 1087 10.1126/science.aad5497 26941318 PMC4887275 · DOI · Paper page
  12. [13]Jang HS Transposable elements drive widespread expression of oncogenes in human cancers Nat. Genet. 2019 51 611 617 10.1038/s41588-019-0373-3 30926969 PMC6443099 · DOI
  13. [14]Chuong EB Elde NC Feschotte C Regulatory activities of transposable elements: from conflicts to benefits Nat. Rev. Genet. 2017 18 71 86 10.1038/nrg.2016.139 27867194 PMC5498291 · DOI
  14. [16]Sundaram V Widespread contribution of transposable elements to the innovation of gene regulatory networks Genome Res. 2014 24 1963 1976 10.1101/gr.168872.113 25319995 PMC4248313 · DOI
  15. [17]Chuong EB Rumi MAK Soares MJ Baker JC Endogenous retroviruses function as species-specific enhancer elements in the placenta Nat. Genet. 2013 45 325 329 10.1038/ng.2553 23396136 PMC3789077 · DOI · Paper page
  16. [18]Todd CD Deniz O Taylor D Branco MR Functional evaluation of transposable elements as enhancers in mouse embryonic and trophoblast stem cells eLife 2019 8 e44344 10.7554/eLife.44344 31012843 PMC6544436 · DOI
  17. [20]Dunn-Fletcher CE Anthropoid primate-specific retroviral element THE1B controls expression of CRH in placenta and alters gestation length PLoS Biol. 2018 16 e2006337 10.1371/journal.pbio.2006337 30231016 PMC6166974 · DOI
  18. [21]Sun, M. et al. Endogenous retroviruses drive lineage-specific regulatory evolution across primate and rodent placentae. Mol. Biol. Evol.10.1093/molbev/msab223 (2021). PMC8557419 34320657 · DOI
  19. [22]Kaya-Okur HS CUT&Tag for efficient epigenomic profiling of small samples and single cells Nat. Commun. 2019 10 1930 10.1038/s41467-019-09982-5 31036827 PMC6488672 · DOI · Paper page
  20. [23]Ashley B Placental uptake and metabolism of 25(OH)vitamin D determine its activity within the fetoplacental unit eLife 2022 11 e71094 10.7554/eLife.71094 35256050 PMC8903835 · DOI
  21. [24]Okae H Derivation of human trophoblast stem cells Cell Stem Cell 2018 22 50 63 10.1016/j.stem.2017.11.004 29249463 · DOI
  22. [25]Kunarso G Transposable elements have rewired the core regulatory network of human embryonic stem cells Nat. Genet. 2010 42 631 634 10.1038/ng.600 20526341 · DOI
  23. [26]Carter T Mosaic cis-regulatory evolution drives transcriptional partitioning of HERVH endogenous retrovirus in the human embryo eLife 2022 11 e76257 10.7554/eLife.76257 35179489 PMC8912925 · DOI
  24. [27]He G p57KIP2‑mediated inhibition of human trophoblast apoptosis and promotion of invasion in vitro Int. J. Mol. Med. 2019 44 281 290 31059007
  25. [28]Kubota K Kent LN Rumi MAK Roby KF Soares MJ Dynamic regulation of AP-1 transcriptional complexes directs trophoblast differentiation Mol. Cell. Biol. 2015 35 3163 3177 10.1128/MCB.00118-15 26149388 PMC4539370 · DOI
  26. [29]Kadam L Kohan-Ghadr HR Drewlo S The balancing act—PPAR-γ’s roles at the maternal-fetal interface Syst. Biol. Reprod. Med. 2015 61 65 71 10.3109/19396368.2014.991881 25475254 PMC6364849 · DOI
  27. [30]Chen H Potential role of FoxO3a in the regulation of trophoblast development and pregnancy complications J. Cell. Mol. Med. 2021 25 4363 4372 10.1111/jcmm.16499 33811439 PMC8093966 · DOI
  28. [31]Skene PJ Henikoff S An efficient targeted nuclease strategy for high-resolution mapping of DNA binding sites eLife 2017 6 e21856 10.7554/eLife.21856 28079019 PMC5310842 · DOI
  29. [32]Chi F Sharpley MS Nagaraj R Roy SS Banerjee U Glycolysis-independent glucose metabolism distinguishes TE from ICM fate during mammalian embryogenesis Dev. Cell 2020 53 9 26 10.1016/j.devcel.2020.02.015 32197068 PMC7289320 · DOI
  30. [33]van de Lagemaat LN Landry J-R Mager DL Medstrand P Transposable elements in mammals promote regulatory variation and diversification of genes with specialized functions Trends Genet. 2003 19 530 536 10.1016/j.tig.2003.08.004 14550626 · DOI · Paper page
  31. [34]Schulte AM Human trophoblast and choriocarcinoma expression of the growth factor pleiotrophin attributable to germ-line insertion of an endogenous retrovirus Proc. Natl Acad. Sci. USA 1996 93 14759 14764 10.1073/pnas.93.25.14759 8962128 PMC26209 · DOI
  32. [35]Emera D Wagner GP Transformation of a transposon into a derived prolactin promoter with function during human pregnancy Proc. Natl Acad. Sci. USA 2012 109 11246 11251 10.1073/pnas.1118566109 22733751 PMC3396485 · DOI
  33. [36]Landry J-R Rouhi A Medstrand P Mager DL The Opitz syndrome gene Mid1 is transcribed from a human endogenous retroviral promoter Mol. Biol. Evol. 2002 19 1934 1942 10.1093/oxfordjournals.molbev.a004017 12411602 · DOI
  34. [37]Teoh PJ Atypical chemokine receptor ACKR2 mediates chemokine scavenging by primary human trophoblasts and can regulate fetal growth, placental structure and neonatal mortality in mice J. Immunol. 2014 193 5218 5228 10.4049/jimmunol.1401096 25297873 · DOI
  35. [38]Dong C Derivation of trophoblast stem cells from naïve human pluripotent stem cells eLife 2020 9 e52504 10.7554/eLife.52504 32048992 PMC7062471 · DOI
  36. [39]Lin TM Halbert SP Spellacy WN Measurement of pregnancy-associated plasma proteins during human gestation J. Clin. Invest. 1974 54 576 582 10.1172/JCI107794 4853116 PMC301590 · DOI
  37. [40]Arnold LL Pregnancy-specific glycoprotein gene expression in recurrent aborters: a potential correlation to interleukin-10 expression Am. J. Reprod. Immunol. 1999 41 174 182 10.1111/j.1600-0897.1999.tb00530.x 10326620 · DOI
  38. [41]Karg NJ Csaba IF Than GN Arany AA Szabó DG The prognosis of the possible foetal and placental complications during delivery by measuring maternal serum levels of pregnancy-specific β-1-glycoprotein (SP1) Arch. Gynecol. 1981 231 69 73 10.1007/BF02110026 6977342 · DOI
  39. [42]Towler CM Horne CH Jandial V Campbell DM MacGillivray I Plasma levels of pregnancy-specific β 1-glycoprotein in complicated pregnancies Br. J. Obstet. Gynaecol. 1977 84 258 263 10.1111/j.1471-0528.1977.tb12573.x 870010 · DOI
  40. [43]Bubici C Papa S JNK signalling in cancer: in need of new, smarter therapeutic targets: JNKs in cancer Br. J. Pharmacol. 2014 171 24 37 10.1111/bph.12432 24117156 PMC3874694 · DOI
  41. [44]Sabapathy K Distinct roles for JNK1 and JNK2 in regulating JNK activity and c-Jun-dependent cell proliferation Mol. Cell 2004 15 713 725 10.1016/j.molcel.2004.08.028 15350216 · DOI
  42. [45]Huh J-W Ha H-S Kim D-S Kim H-S Placenta-restricted expression of LTR-derived NOS3 Placenta 2008 29 602 608 10.1016/j.placenta.2008.04.002 18474398 · DOI
  43. [47]Carter AM Pijnenborg R Evolution of invasive placentation with special reference to non-human primates Best Pract. Res. Clin. Obstet. Gynaecol. 2011 25 249 257 10.1016/j.bpobgyn.2010.10.010 21056010 · DOI
  44. [48]Schmidt JK Placenta-derived macaque trophoblast stem cells: differentiation to syncytiotrophoblasts and extravillous trophoblasts reveals phenotypic reprogramming Sci. Rep. 2020 10 19159 10.1038/s41598-020-76313-w 33154556 PMC7644694 · DOI
  45. [49]Luo Y Kumar P Mendelson CR Estrogen-related receptor γ (ERRγ) regulates oxygen-dependent expression of voltage-gated potassium (K+) channels and tissue kallikrein during human trophoblast differentiation Mol. Endocrinol. 2013 27 940 952 10.1210/me.2013-1038 23584901 PMC3656234 · DOI
  46. [50]Zhang X Stomatin-like protein 2 (SLP2) regulates the proliferation and invasion of trophoblast cells by modulating mitochondrial functions Placenta 2020 100 13 23 10.1016/j.placenta.2020.07.008 32814233 · DOI
  47. [51]Kuales G Weiss M Sedelmeier O Pfeifer D Arnold SJ A resource for the transcriptional signature of bona fide trophoblast stem cells and analysis of their embryonic persistence Stem Cells Int 2015 2015 218518 10.1155/2015/218518 26783396 PMC4691490 · DOI
  48. [52]Wang H Leptin-promoted human extravillous trophoblast invasion is MMP14 dependent and requires the cross talk between Notch1 and PI3K/Akt signaling Biol. Reprod. 2014 90 78 10.1095/biolreprod.113.114876 24571988 · DOI
  49. [53]Kim JD Rex1/Zfp42 as an epigenetic regulator for genomic imprinting Hum. Mol. Genet. 2011 20 1353 1362 10.1093/hmg/ddr017 21233130 PMC3049358 · DOI
  50. [54]Rogers MB Hosler BA Gudas LJ Specific expression of a retinoic acid-regulated, zinc-finger gene, Rex-1, in preimplantation embryos, trophoblast and spermatocytes Development 1991 113 815 824 10.1242/dev.113.3.815 1821852 · DOI
  51. [55]Deniz Ö Endogenous retroviruses are a source of enhancers with oncogenic potential in acute myeloid leukaemia Nat. Commun. 2020 11 3506 10.1038/s41467-020-17206-4 32665538 PMC7360734 · DOI
  52. [56]Ahmed SIY Ibrahim ME Khalil EAG High altitude and pre-eclampsia: adaptation or protection Med. Hypotheses 2017 104 128 132 10.1016/j.mehy.2017.05.007 28673571 · DOI
  53. [57]Chou C-W Huang Y-K Kuo T-T Liu J-P Sher Y-P An overview of ADAM9: structure, activation and regulation in human diseases Int. J. Mol. Sci. 2020 21 E7790 10.3390/ijms21207790 PMC7590139 33096780 · DOI
  54. [58]Inagaki A Upregulation of HtrA4 in the placentas of patients with severe pre-eclampsia Placenta 2012 33 919 926 10.1016/j.placenta.2012.08.003 22964307 · DOI
  55. [59]Singh H Human HtrA4 expression is restricted to the placenta, is significantly up-regulated in early-onset preeclampsia, and high levels of HtrA4 cause endothelial dysfunction J. Clin. Endocrinol. Metab. 2015 100 E936 E945 10.1210/jc.2014-3969 25946029 · DOI
  56. [60]Visvader J Verma IM Differential transcription of exon 1 of the human c-fms gene in placental trophoblasts and monocytes Mol. Cell. Biol. 1989 9 1336 1341 2524648 PMC362728
  57. [61]Kauma SW Aukerman SL Eierman D Turner T Colony-stimulating factor-1 and c-fms expression in human endometrial tissues and placenta during the menstrual cycle and early pregnancy J. Clin. Endocrinol. Metab. 1991 73 746 751 10.1210/jcem-73-4-746 1832423 · DOI
  58. [62]Ahmad SF Targeting colony stimulating factor-1 receptor signalling to treat ectopic pregnancy Sci. Rep. 2020 10 15638 10.1038/s41598-020-72785-y 32973322 PMC7519033 · DOI
  59. [63]Hamilton GS Lysiak JJ Watson AJ Lala PK Effects of colony stimulating factor-1 on human extravillous trophoblast growth and invasion J. Endocrinol. 1998 159 69 77 10.1677/joe.0.1590069 9795343 · DOI
  60. [64]Pollard JW Apparent role of the macrophage growth factor, CSF-1, in placental development Nature 1987 330 484 486 10.1038/330484a0 2446141 · DOI
  61. [65]Hayashi M Ohkura T Inaba N Elevation of serum macrophage colony-stimulating factor before the clinical manifestations of preeclampsia Am. J. Obstet. Gynecol. 2003 189 1356 1360 10.1067/S0002-9378(03)00674-4 14634568 · DOI
  62. [66]Lu X Twist1 is involved in trophoblast syncytialization by regulating GCM1 Placenta 2016 39 45 54 10.1016/j.placenta.2016.01.008 26992674 · DOI
  63. [67]Ng YH Zhu H Leung PCK Twist regulates cadherin-mediated differentiation and fusion of human trophoblastic cells J. Clin. Endocrinol. Metab. 2011 96 3881 3890 10.1210/jc.2010-2714 21994965 · DOI
  64. [68]Qin Q Xu Y He T Qin C Xu J Normal and disease-related biological functions of Twist1 and underlying molecular mechanisms Cell. Res. 2012 22 90 106 10.1038/cr.2011.144 21876555 PMC3351934 · DOI
  65. [69]Camolotto S Expression and transcriptional regulation of individual pregnancy-specific glycoprotein genes in differentiating trophoblast cells Placenta 2010 31 312 319 10.1016/j.placenta.2010.01.004 20116096 · DOI
  66. [71]Leaños-Miranda A Soluble endoglin as a marker for preeclampsia, its severity, and the occurrence of adverse outcomes Hypertension 2019 74 991 997 10.1161/HYPERTENSIONAHA.119.13348 31446801 · DOI
  67. [72]Caniggia I Taylor CV Ritchie JW Lye SJ Letarte M Endoglin regulates trophoblast differentiation along the invasive pathway in human placental villous explants Endocrinology 1997 138 4977 4988 10.1210/endo.138.11.5475 9348229 · DOI
  68. [73]Mano Y The loss of endoglin promotes the invasion of extravillous trophoblasts Endocrinology 2011 152 4386 4394 10.1210/en.2011-1088 21914777 · DOI
  69. [74]Zhang B Human placental cytotrophoblast epigenome dynamics over gestation and alterations in placental disease Dev. Cell 2021 56 1238 1252 10.1016/j.devcel.2021.04.001 33891899 PMC8650129 · DOI
  70. [75]Ivancevic, A., Simpson, D. M. & Chuong, E. B. Endogenous retroviruses mediate transcriptional rewiring in response to oncogenic signaling in colorectal cancer. Preprint at https://www.biorxiv.org/content/10.1101/2021.10.28.466196v2 (2021). PMC466953 39018396 · DOI
  71. [77]Costanzo V Bardelli A Siena S Abrignani S Exploring the links between cancer and placenta development Open Biol. 2018 8 180081 10.1098/rsob.180081 29950452 PMC6030113 · DOI
  72. [78]Meinhardt G Pivotal role of the transcriptional co-activator YAP in trophoblast stemness of the developing human placenta Proc. Natl Acad. Sci. USA 2020 117 13562 13570 10.1073/pnas.2002630117 32482863 PMC7306800 · DOI
  73. [79]Zimmermann W Kammerer R The immune-modulating pregnancy-specific glycoproteins evolve rapidly and their presence correlates with hemochorial placentation in primates BMC Genomics 2021 22 128 10.1186/s12864-021-07413-8 33602137 PMC7893922 · DOI
  74. [80]Rudert F Zimmermann W Thompson JA Intra- and interspecies analyses of the carcinoembryonic antigen (CEA) gene family reveal independent evolution in primates and rodents J. Mol. Evol. 1989 29 126 134 10.1007/BF02100111 2509715 · DOI
  75. [81]Li Y Moretto-Zita M Leon-Garcia S Parast MM p63 inhibits extravillous trophoblast migration and maintains cells in a cytotrophoblast stem cell-like state Am. J. Pathol. 2014 184 3332 3343 10.1016/j.ajpath.2014.08.006 25307348 PMC4258507 · DOI
  76. [82]Riege K Dissecting the DNA binding landscape and gene regulatory network of p63 and p53 eLife 2020 9 e63266 10.7554/eLife.63266 33263276 PMC7735755 · DOI
  77. [83]Su D Interactions of chromatin context, binding site sequence content, and sequence evolution in stress-induced p53 occupancy and transactivation PLoS Genet. 2015 11 e1004885 10.1371/journal.pgen.1004885 25569532 PMC4287438 · DOI
  78. [84]Seligman SP Buyon JP Clancy RM Young BK Abramson SB The role of nitric oxide in the pathogenesis of preeclampsia Am. J. Obstet. Gynecol. 1994 171 944 948 10.1016/S0002-9378(94)70064-8 7943106 · DOI
  79. [85]Abbas Y Turco MY Burton GJ Moffett A Investigation of human trophoblast invasion in vitro Hum. Reprod. Update 2020 26 501 513 10.1093/humupd/dmaa017 32441309 PMC7473396 · DOI
  80. [86]Ojosnegros S Seriola A Godeau AL Veiga A Embryo implantation in the laboratory: an update on current techniques Hum. Reprod. Update 2021 27 501 530 10.1093/humupd/dmaa054 33410481 · DOI
  81. [87]Takahashi S Loss of p57KIP2 expression confers resistance to contact inhibition in human androgenetic trophoblast stem cells Proc. Natl Acad. Sci. USA 2019 116 26606 26613 10.1073/pnas.1916019116 31792181 PMC6936680 · DOI
  82. [88]Langmead B Salzberg SL Fast gapped-read alignment with Bowtie 2 Nat. Methods 2012 9 357 359 10.1038/nmeth.1923 22388286 PMC3322381 · DOI · Paper page
  83. [89]Kim D Paggi JM Park C Bennett C Salzberg SL Graph-based genome alignment and genotyping with HISAT2 and HISAT-genotype Nat. Biotechnol. 2019 37 907 915 10.1038/s41587-019-0201-4 31375807 PMC7605509 · DOI · Paper page
  84. [90]Ramírez F deepTools2: a next generation web server for deep-sequencing data analysis Nucleic Acids Res. 2016 44 W160 W165 10.1093/nar/gkw257 27079975 PMC4987876 · DOI · Paper page
  85. [91]Zhang Y Model-based analysis of ChIP-Seq (MACS) Genome Biol. 2008 9 R137 10.1186/gb-2008-9-9-r137 18798982 PMC2592715 · DOI · Paper page
  86. [93]Love MI Huber W Anders S Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2 Genome Biol. 2014 15 550 10.1186/s13059-014-0550-8 25516281 PMC4302049 · DOI · Paper page
  87. [94]Yang WR Ardeljan D Pacyna CN Payer LM Burns KH SQuIRE reveals locus-specific regulation of interspersed repeat expression Nucleic Acids Res. 2019 47 e27 10.1093/nar/gky1301 30624635 PMC6411935 · DOI
  88. [95]Bailey TL Johnson J Grant CE Noble WS The MEME Suite Nucleic Acids Res. 2015 43 W39 W49 10.1093/nar/gkv416 25953851 PMC4489269 · DOI
  89. [96]Pertea M StringTie enables improved reconstruction of a transcriptome from RNA-seq reads Nat. Biotechnol. 2015 33 290 295 10.1038/nbt.3122 25690850 PMC4643835 · DOI

Cited by

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Authors
Frost, J. M., Amante, S. M., Okae, H., Jones, E. M., Ashley, B., Lewis, R. M., Cleal, J. K., Caley, M. P., Arima, T., Maffucci, T., & Branco, M. R.
Affiliations
  • Queen Mary University of London (GB)
  • Institute of Molecular Embryology and Genetics, Kumamoto University (JP)
  • University of Southampton (GB)
  • Tohoku University (JP)
Corresponding author
  • Frost, Jennifer M.
  • Branco, Miguel R.
ORCID
Venue
Nature Structural & Molecular Biology
Publisher
Springer Science and Business Media LLC
Published
2023-04
Volume
30
Issue
4
Pages
527-538
ISSN
  • 1545-9985 (ISSN-L)
  • 1545-9993
DOI
10.1038/s41594-023-00960-6
PMC
PMC10113160
OpenAlex
W4362524050
Cited by
94
References
7
Citations by year
2026: 20 · 2025: 35 · 2024: 24 · 2023: 15
FWCI
14.81
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature Structural & Molecular Biology (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by)
  • Research Square (acceptedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • ePrints Soton (University of Southampton) (submittedVersion)
  • Queen Mary Research Online (Queen Mary University of London) (submittedVersion, cc-by)
Funders
  • Leakey Foundation
  • Barts Charity
  • European Commission (HORIZON2020, 841172)
  • Medical Research Council
  • Biotechnology and Biological Sciences Research Council (BB/T000031/1)
  • Japan Society for the Promotion of Science (19H05757, 21H03072, 21K19546, 21H04834)
Topics
  • Life Sciences › Agricultural and Biological Sciences › Plant Science › Chromosomal and Genetic Variations
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
  • Life Sciences › Immunology and Microbiology › Immunology › Reproductive System and Pregnancy
Keywords
endogenous retroviruses, transposable elements, placental evolution, enhancers, CSF1R, ENG, soluble endoglin, preeclampsia, transcription factor binding, epigenomics, trophoblast stem cells
MeSH terms
Animals, DNA Transposable Elements, Female, Gene Expression Regulation, Humans, Placenta, Pregnancy, Trophoblasts, Gene Expression, Endogenous Retroviruses

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