The Epigenomic Landscape of Transposable Elements Across Normal Human Development and Anatomy

Overview

Journal Nat Commun

Specialty Biology

Date 2019 Dec 12

PMID 31822674

Citations 48

Authors

Erica C Pehrsson

Mayank N K Choudhary

Vasavi Sundaram

Ting Wang

Affiliations

Soon will be listed here.

Abstract

Transposable elements (TEs) have deposited functional regulatory elements throughout the human genome. Although most are silenced, certain TEs have been co-opted by the host. However, a comprehensive, multidimensional picture of the contribution of TEs to normal human gene regulation is still lacking. Here, we quantify the epigenomic status of TEs across human anatomy and development using data from the Roadmap Epigenomics Project. We find that TEs encompass a quarter of the human regulatory epigenome, and 47% of elements can be in an active regulatory state. We demonstrate that SINEs are enriched relative to other classes for active and transcribed marks, that TEs encompass a higher proportion of enhancer states in the hematopoietic lineage, and that DNA methylation of Alu elements decreases with age, corresponding with a loss of CpG islands. Finally, we identify TEs that may perform an evolutionarily conserved regulatory function, providing a systematic profile of TE activity in normal human tissue.

Citing Articles

Activation of endogenous retroviruses and induction of viral mimicry by MEK1/2 inhibition in pancreatic cancer.

Cortesi A, Gandolfi F, Arco F, Di Chiaro P, Valli E, Polletti S Sci Adv. 2024; 10(13):eadk5386.

PMID: 38536927 PMC: 10971493. DOI: 10.1126/sciadv.adk5386.

Locus-level L1 DNA methylation profiling reveals the epigenetic and transcriptional interplay between L1s and their integration sites.

Lanciano S, Philippe C, Sarkar A, Pratella D, Domrane C, Doucet A Cell Genom. 2024; 4(2):100498.

PMID: 38309261 PMC: 10879037. DOI: 10.1016/j.xgen.2024.100498.

Fine-Scale Map Reveals Highly Variable Recombination Rates Associated with Genomic Features in the Eurasian Blackcap.

Bascon-Cardozo K, Bours A, Manthey G, Durieux G, Dutheil J, Pruisscher P Genome Biol Evol. 2024; 16(1).

PMID: 38198800 PMC: 10781513. DOI: 10.1093/gbe/evad233.

Statistical learning quantifies transposable element-mediated cis-regulation.

Pulver C, Grun D, Duc J, Sheppard S, Planet E, Coudray A Genome Biol. 2023; 24(1):258.

PMID: 37950299 PMC: 10637000. DOI: 10.1186/s13059-023-03085-7.

Isoform-resolved transcriptome of the human preimplantation embryo.

Torre D, Francoeur N, Kalma Y, Gross Carmel I, Melo B, Deikus G Nat Commun. 2023; 14(1):6902.

PMID: 37903791 PMC: 10616205. DOI: 10.1038/s41467-023-42558-y.

References

Azad N, Zahnow C, Rudin C, Baylin S . The future of epigenetic therapy in solid tumours--lessons from the past. Nat Rev Clin Oncol. 2013; 10(5):256-66. PMC: 3730253. DOI: 10.1038/nrclinonc.2013.42. View

Bejerano G, Lowe C, Ahituv N, King B, Siepel A, Salama S . A distal enhancer and an ultraconserved exon are derived from a novel retroposon. Nature. 2006; 441(7089):87-90. DOI: 10.1038/nature04696. View

Bourque G, Leong B, Vega V, Chen X, Lee Y, Srinivasan K . Evolution of the mammalian transcription factor binding repertoire via transposable elements. Genome Res. 2008; 18(11):1752-62. PMC: 2577865. DOI: 10.1101/gr.080663.108. View

St Laurent G, Shtokalo D, Dong B, Tackett M, Fan X, Lazorthes S . VlincRNAs controlled by retroviral elements are a hallmark of pluripotency and cancer. Genome Biol. 2013; 14(7):R73. PMC: 4053963. DOI: 10.1186/gb-2013-14-7-r73. View

Djebali S, Davis C, Merkel A, Dobin A, Lassmann T, Mortazavi A . Landscape of transcription in human cells. Nature. 2012; 489(7414):101-8. PMC: 3684276. DOI: 10.1038/nature11233. View

Chuong E, Elde N, Feschotte C . Regulatory evolution of innate immunity through co-option of endogenous retroviruses. Science. 2016; 351(6277):1083-7. PMC: 4887275. DOI: 10.1126/science.aad5497. View

Yue F, Cheng Y, Breschi A, Vierstra J, Wu W, Ryba T . A comparative encyclopedia of DNA elements in the mouse genome. Nature. 2014; 515(7527):355-64. PMC: 4266106. DOI: 10.1038/nature13992. View

Sasaki T, Nishihara H, Hirakawa M, Fujimura K, Tanaka M, Kokubo N . Possible involvement of SINEs in mammalian-specific brain formation. Proc Natl Acad Sci U S A. 2008; 105(11):4220-5. PMC: 2393765. DOI: 10.1073/pnas.0709398105. View

Friedli M, Trono D . The developmental control of transposable elements and the evolution of higher species. Annu Rev Cell Dev Biol. 2015; 31:429-51. DOI: 10.1146/annurev-cellbio-100814-125514. View

10.

Kunarso G, Chia N, Jeyakani J, Hwang C, Lu X, Chan Y . Transposable elements have rewired the core regulatory network of human embryonic stem cells. Nat Genet. 2010; 42(7):631-4. DOI: 10.1038/ng.600. View

11.

Xie M, Hong C, Zhang B, Lowdon R, Xing X, Li D . DNA hypomethylation within specific transposable element families associates with tissue-specific enhancer landscape. Nat Genet. 2013; 45(7):836-41. PMC: 3695047. DOI: 10.1038/ng.2649. View

12.

Wang J, Vicente-Garcia C, Seruggia D, Molto E, Fernandez-Minan A, Neto A . MIR retrotransposon sequences provide insulators to the human genome. Proc Natl Acad Sci U S A. 2015; 112(32):E4428-37. PMC: 4538669. DOI: 10.1073/pnas.1507253112. View

13.

Baylin S, Jones P . Epigenetic Determinants of Cancer. Cold Spring Harb Perspect Biol. 2016; 8(9). PMC: 5008069. DOI: 10.1101/cshperspect.a019505. View

14.

Goke J, Lu X, Chan Y, Ng H, Ly L, Sachs F . Dynamic transcription of distinct classes of endogenous retroviral elements marks specific populations of early human embryonic cells. Cell Stem Cell. 2015; 16(2):135-41. DOI: 10.1016/j.stem.2015.01.005. View

15.

Jacques P, Jeyakani J, Bourque G . The majority of primate-specific regulatory sequences are derived from transposable elements. PLoS Genet. 2013; 9(5):e1003504. PMC: 3649963. DOI: 10.1371/journal.pgen.1003504. View

16.

Sundaram V, Choudhary M, Pehrsson E, Xing X, Fiore C, Pandey M . Functional cis-regulatory modules encoded by mouse-specific endogenous retrovirus. Nat Commun. 2017; 8:14550. PMC: 5379053. DOI: 10.1038/ncomms14550. View

17.

Kundaje A, Meuleman W, Ernst J, Bilenky M, Yen A, Heravi-Moussavi A . Integrative analysis of 111 reference human epigenomes. Nature. 2015; 518(7539):317-30. PMC: 4530010. DOI: 10.1038/nature14248. View

18.

Britten R, Davidson E . Repetitive and non-repetitive DNA sequences and a speculation on the origins of evolutionary novelty. Q Rev Biol. 1971; 46(2):111-38. DOI: 10.1086/406830. View

19.

. An integrated encyclopedia of DNA elements in the human genome. Nature. 2012; 489(7414):57-74. PMC: 3439153. DOI: 10.1038/nature11247. View

20.

Wang T, Zeng J, Lowe C, Sellers R, Salama S, Yang M . Species-specific endogenous retroviruses shape the transcriptional network of the human tumor suppressor protein p53. Proc Natl Acad Sci U S A. 2007; 104(47):18613-8. PMC: 2141825. DOI: 10.1073/pnas.0703637104. View