Transposable Elements Have Rewired the Core Regulatory Network of Human Embryonic Stem Cells

Overview

Journal Nat Genet

Specialty Genetics

Date 2010 Jun 8

PMID 20526341

Citations 441

Authors

Galih Kunarso

Na-Yu Chia

Justin Jeyakani

Catalina Hwang

Xinyi Lu

Yun-Shen Chan

Huck-Hui Ng

Guillaume Bourque

Affiliations

Soon will be listed here.

Abstract

Detection of new genomic control elements is critical in understanding transcriptional regulatory networks in their entirety. We studied the genome-wide binding locations of three key regulatory proteins (POU5F1, also known as OCT4; NANOG; and CTCF) in human and mouse embryonic stem cells. In contrast to CTCF, we found that the binding profiles of OCT4 and NANOG are markedly different, with only approximately 5% of the regions being homologously occupied. We show that transposable elements contributed up to 25% of the bound sites in humans and mice and have wired new genes into the core regulatory network of embryonic stem cells. These data indicate that species-specific transposable elements have substantially altered the transcriptional circuitry of pluripotent stem cells.

Citing Articles

An appropriate DNA input for bisulfite conversion reveals LINE-1 and Alu hypermethylation in tissues and circulating cell-free DNA from cancers.

Tran T, Pham T, Nguyen T, Hien Do T, Luu P, Nguyen U PLoS One. 2025; 19(12):e0316394.

PMID: 39775734 PMC: 11684646. DOI: 10.1371/journal.pone.0316394.

LINE-1-Induced Retrotransposition Affects Early Preimplantation Embryo DNA Integrity and Pluripotency.

Sakaloglou P, Lazaros L, Bouba I, Markoula S, Zikopoulos A, Drakaki E Int J Mol Sci. 2024; 25(23).

PMID: 39684434 PMC: 11641028. DOI: 10.3390/ijms252312722.

Extensive binding of uncharacterized human transcription factors to genomic dark matter.

Razavi R, Fathi A, Yellan I, Brechalov A, Laverty K, Jolma A bioRxiv. 2024; .

PMID: 39605320 PMC: 11601254. DOI: 10.1101/2024.11.11.622123.

Impact of endogenous viral elements on glioma clinical phenotypes by inducing OCT4 in the host.

Li S, He S, Xue H, He Y Front Cell Infect Microbiol. 2024; 14:1474492.

PMID: 39588508 PMC: 11586349. DOI: 10.3389/fcimb.2024.1474492.

Functional Bidirectionality of ERV-Derived Long Non-Coding RNAs in Humans.

Song Y, Wen H, Zhai X, Jia L, Li L Int J Mol Sci. 2024; 25(19).

PMID: 39408810 PMC: 11476766. DOI: 10.3390/ijms251910481.

References

Dermitzakis E, Clark A . Evolution of transcription factor binding sites in Mammalian gene regulatory regions: conservation and turnover. Mol Biol Evol. 2002; 19(7):1114-21. DOI: 10.1093/oxfordjournals.molbev.a004169. View

Birney E, Stamatoyannopoulos J, Dutta A, Guigo R, Gingeras T, Margulies E . Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project. Nature. 2007; 447(7146):799-816. PMC: 2212820. DOI: 10.1038/nature05874. View

Thomson J, Itskovitz-Eldor J, Shapiro S, Waknitz M, Swiergiel J, Marshall V . Embryonic stem cell lines derived from human blastocysts. Science. 1998; 282(5391):1145-7. DOI: 10.1126/science.282.5391.1145. View

Boyer L, Lee T, Cole M, Johnstone S, Levine S, Zucker J . Core transcriptional regulatory circuitry in human embryonic stem cells. Cell. 2005; 122(6):947-56. PMC: 3006442. DOI: 10.1016/j.cell.2005.08.020. View

Siepel A, Bejerano G, Pedersen J, Hinrichs A, Hou M, Rosenbloom K . Evolutionarily conserved elements in vertebrate, insect, worm, and yeast genomes. Genome Res. 2005; 15(8):1034-50. PMC: 1182216. DOI: 10.1101/gr.3715005. View

Feschotte C . Transposable elements and the evolution of regulatory networks. Nat Rev Genet. 2008; 9(5):397-405. PMC: 2596197. DOI: 10.1038/nrg2337. View

Tesar P, Chenoweth J, Brook F, Davies T, Evans E, Mack D . New cell lines from mouse epiblast share defining features with human embryonic stem cells. Nature. 2007; 448(7150):196-9. DOI: 10.1038/nature05972. View

Rossant J . Stem cells and early lineage development. Cell. 2008; 132(4):527-31. DOI: 10.1016/j.cell.2008.01.039. View

Brosius J . Retroposons--seeds of evolution. Science. 1991; 251(4995):753. DOI: 10.1126/science.1990437. View

10.

Kim T, Abdullaev Z, Smith A, Ching K, Loukinov D, Green R . Analysis of the vertebrate insulator protein CTCF-binding sites in the human genome. Cell. 2007; 128(6):1231-45. PMC: 2572726. DOI: 10.1016/j.cell.2006.12.048. View

11.

McCLINTOCK B . The significance of responses of the genome to challenge. Science. 1984; 226(4676):792-801. DOI: 10.1126/science.15739260. View

12.

Bell A, West A, Felsenfeld G . The protein CTCF is required for the enhancer blocking activity of vertebrate insulators. Cell. 1999; 98(3):387-96. DOI: 10.1016/s0092-8674(00)81967-4. View

13.

Davidson E, Britten R . Regulation of gene expression: possible role of repetitive sequences. Science. 1979; 204(4397):1052-9. DOI: 10.1126/science.451548. View

14.

Brons I, Smithers L, Trotter M, Rugg-Gunn P, Sun B, Chuva de Sousa Lopes S . Derivation of pluripotent epiblast stem cells from mammalian embryos. Nature. 2007; 448(7150):191-5. DOI: 10.1038/nature05950. View

15.

Borneman A, Gianoulis T, Zhang Z, Yu H, Rozowsky J, Seringhaus M . Divergence of transcription factor binding sites across related yeast species. Science. 2007; 317(5839):815-9. DOI: 10.1126/science.1140748. View

16.

Xu C, Inokuma M, Denham J, Golds K, Kundu P, Gold J . Feeder-free growth of undifferentiated human embryonic stem cells. Nat Biotechnol. 2001; 19(10):971-4. DOI: 10.1038/nbt1001-971. View

17.

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

18.

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

19.

Cao R, Zhang Y . SUZ12 is required for both the histone methyltransferase activity and the silencing function of the EED-EZH2 complex. Mol Cell. 2004; 15(1):57-67. DOI: 10.1016/j.molcel.2004.06.020. View

20.

Odom D, Dowell R, Jacobsen E, Gordon W, Danford T, MacIsaac K . Tissue-specific transcriptional regulation has diverged significantly between human and mouse. Nat Genet. 2007; 39(6):730-2. PMC: 3797512. DOI: 10.1038/ng2047. View