The DOI matches its Crossref record; 13 of the 13 references it cites were found in a registry or an index.
Endogenous retroviruses and neighboring genes are coordinately repressed by LSD1/KDM1A
Open accessAbstract
Endogenous retroviruses (ERVs) constitute a substantial portion of mammalian genomes, and their retrotransposition activity helped to drive genetic variation, yet their expression is tightly regulated to prevent unchecked amplification. We generated a series of mouse mutants and embryonic stem (ES) cell lines carrying “deletable” and “rescuable” alleles of the lysine-specific demethylase LSD1/KDM1A. In the absence of KDM1A, the murine endogenous retrovirus MuERV-L/MERVL becomes overexpressed and embryonic development arrests at gastrulation. A number of cellular genes normally restricted to the zygotic genome activation (ZGA) period also become up-regulated in Kdm1a mutants. Strikingly, many of these cellular genes are flanked by MERVL sequences or have cryptic LTRs as promoters that are targets of KDM1A repression. Using genome-wide epigenetic profiling of Kdm1a mutant ES cells, we demonstrate that this subset of ZGA genes and MERVL elements displays increased methylation of histone H3K4, increased acetylation of H3K27, and decreased methylation of H3K9. As a consequence, Kdm1a mutant ES cells exhibit an unusual propensity to generate extraembryonic tissues. Our findings suggest that ancient retroviral insertions were used to co-opt regulatory sequences targeted by KDM1A for epigenetic silencing of cell fate genes during early mammalian embryonic development.
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Citations
Cites
Initial sequencing and comparative analysis of the mouse genome
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A bivalent chromatin structure marks key developmental genes in embryonic stem cells
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Human DNA methylomes at base resolution show widespread epigenomic differences
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Self-citationGenome-wide maps of chromatin state in pluripotent and lineage-committed cells
Mikkelsen, T. S., Ku, M., Jaffe, D. B., Issac, B., Lieberman, E., Giannoukos, G., Alvarez, P., Brockman, W., Kim, T.-K., Koche, R. P., et al. (2007) · Nature · doi:10.1038/nature06008 · Cited by 4,129
Histone demethylation mediated by the nuclear amine oxidase homolog LSD1
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Targeted mutation of the DNA methyltransferase gene results in embryonic lethality
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Self-citationHistone modifications at human enhancers reflect global cell-type-specific gene expression
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Self-citationStability and flexibility of epigenetic gene regulation in mammalian development
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“The long-term silencing of REs has been attributed to DNA CpG methylation (Reik 2007).”
BackgroundKAP1 controls endogenous retroviruses in embryonic stem cells
Rowe, H. M., Jakobsson, J., Mesnard, D., Rougemont, J., Reynard, S., Aktas, T., Maillard, P. V., Layard-Liesching, H., Verp, S., Marquis, J., et al. (2010) · Nature · doi:10.1038/nature08674 · Cited by 874
Cited by
SMARCAD1 ATPase activity is required to silence endogenous retroviruses in embryonic stem cells
Sachs, P., Ding, D., Bergmaier, P., Lamp, B., Schlagheck, C., Finkernagel, F., Nist, A., Stiewe, T., & Mermoud, J. E. (2019) · Nature Communications · doi:10.1038/s41467-019-09078-0 · Cited by 2,384
Embryonic stem cell potency fluctuates with endogenous retrovirus activity
Macfarlan, T. S., Gifford, W. D., Driscoll, S., Lettieri, K., Rowe, H. M., Bonanomi, D., Firth, A., Singer, O., Trono, D., & Pfaff, S. L. (2012) · Nature · doi:10.1038/nature11244 · Cited by 981
Self-citationBuganim, Y., Faddah, D. A., Cheng, A. W., Itskovich, E., Markoulaki, S., Ganz, K., Klemm, S. L., van Oudenaarden, A., & Jaenisch, R. (2012) · Cell · doi:10.1016/j.cell.2012.08.023 · Cited by 793
Hendrickson, P. G., Doráis, J. A., Grow, E. J., Whiddon, J. L., Lim, J.-W., Wike, C. L., Weaver, B. D., Pflueger, C., Emery, B. R., Wilcox, A. L., et al. (2017) · Nature Genetics · doi:10.1038/ng.3844 · Cited by 734
LSD1 Ablation Stimulates Anti-tumor Immunity and Enables Checkpoint Blockade
Sheng, W., LaFleur, M. W., Nguyen, T. H., Chen, S., Chakravarthy, A., Conway, J. R., Li, Y., Chen, H., Yang, H., Hsu, P.-H., et al. (2018) · Cell · doi:10.1016/j.cell.2018.05.052 · Cited by 693
Metadata
- Authors
- Macfarlan, T. S., Gifford, W. D., Agarwal, S., Driscoll, S., Lettieri, K., Wang, J., Andrews, S. E., Franco, L., Rosenfeld, M. G., Ren, B., & Pfaff, S. L.
- Venue
- Genes & Development
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2011-02-28
- Volume
- 25
- Issue
- 6
- Pages
- 594-607
- ISSN
- 0890-9369 (ISSN-L)
- 1549-5477
- OpenAlex
- W2142396207
- Cited by
- 279
- References
- 13
- Type
- posted content
- Language
- en
- Open access
- diamond
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- Macfarlan, T. S., Gifford, W. D., Agarwal, S., Driscoll, S., Lettieri, K., Wang, J., Andrews, S. E., Franco, L., Rosenfeld, M. G., Ren, B., & Pfaff, S. L. (2011). Endogenous retroviruses and neighboring genes are coordinately repressed by LSD1/KDM1A. Genes & Development. https://doi.org/10.1101/gad.2008511
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