Transposable Elements Activation Triggers Necroptosis in Mouse Embryonic Stem Cells

Overview

Journal Cell Death Dis

Specialties Cell Biology
General Medicine

Date 2023 Mar 7

PMID 36882393

Authors

Lingmei Jin

Jiangping He

Huijian Feng

Sa Li

He Liu

Hongzhi Dong

Mingli Hu

Junju Huang

Haoyu Wu

Jiekai Chen

Ling Qi

Kaixin Wu

Affiliations

Soon will be listed here.

Abstract

Deficiency of the histone H3K9 methyltransferase SETDB1 induces RIPK3-dependent necroptosis in mouse embryonic stem cells (mESCs). However, how necroptosis pathway is activated in this process remains elusive. Here we report that the reactivation of transposable elements (TEs) upon SETDB1 knockout is responsible for the RIPK3 regulation through both cis and trans mechanisms. IAPLTR2_Mm and MMERVK10c-int, both of which are suppressed by SETDB1-dependent H3K9me3, act as enhancer-like cis-regulatory elements and their RIPK3 nearby members enhance RIPK3 expression when SETDB1 is knockout. Moreover, reactivated endogenous retroviruses generate excessive viral mimicry, which promotes necroptosis mainly through Z-DNA-binding protein 1 (ZBP1). These results indicate TEs play an important role in regulating necroptosis.

Citing Articles

Identification and clinical implications of endogenous retrovirus elements suppressed by SETDB1 in hepatocellular carcinoma.

Igarashi Y, Akiyama Y, Shimada S, Watanabe S, Hatano M, Kodera K JHEP Rep. 2025; 7(3):101307.

PMID: 40059971 PMC: 11889587. DOI: 10.1016/j.jhepr.2024.101307.

References

Weinlich R, Oberst A, Beere H, Green D . Necroptosis in development, inflammation and disease. Nat Rev Mol Cell Biol. 2016; 18(2):127-136. DOI: 10.1038/nrm.2016.149. View

Bourque G, Burns K, Gehring M, Gorbunova V, Seluanov A, Hammell M . Ten things you should know about transposable elements. Genome Biol. 2018; 19(1):199. PMC: 6240941. DOI: 10.1186/s13059-018-1577-z. View

Takeuchi O, Akira S . Pattern recognition receptors and inflammation. Cell. 2010; 140(6):805-20. DOI: 10.1016/j.cell.2010.01.022. View

Wu K, Liu H, Wang Y, He J, Xu S, Chen Y . SETDB1-Mediated Cell Fate Transition between 2C-Like and Pluripotent States. Cell Rep. 2020; 30(1):25-36.e6. DOI: 10.1016/j.celrep.2019.12.010. View

Matsui T, Leung D, Miyashita H, Maksakova I, Miyachi H, Kimura H . Proviral silencing in embryonic stem cells requires the histone methyltransferase ESET. Nature. 2010; 464(7290):927-31. DOI: 10.1038/nature08858. View

Vandenabeele P, Declercq W, Van Herreweghe F, Vanden Berghe T . The role of the kinases RIP1 and RIP3 in TNF-induced necrosis. Sci Signal. 2010; 3(115):re4. DOI: 10.1126/scisignal.3115re4. View

Khodarev N . Intracellular RNA Sensing in Mammalian Cells: Role in Stress Response and Cancer Therapies. Int Rev Cell Mol Biol. 2019; 344:31-89. DOI: 10.1016/bs.ircmb.2018.08.005. View

Lu J, Walsh C . Programmed necrosis and autophagy in immune function. Immunol Rev. 2012; 249(1):205-17. PMC: 4030387. DOI: 10.1111/j.1600-065X.2012.01147.x. View

Shapiro J . Exploring the read-write genome: mobile DNA and mammalian adaptation. Crit Rev Biochem Mol Biol. 2016; 52(1):1-17. DOI: 10.1080/10409238.2016.1226748. View

10.

Simonti C, Pavlicev M, Capra J . Transposable Element Exaptation into Regulatory Regions Is Rare, Influenced by Evolutionary Age, and Subject to Pleiotropic Constraints. Mol Biol Evol. 2017; 34(11):2856-2869. PMC: 5850124. DOI: 10.1093/molbev/msx219. View

11.

Kapitonov V, Jurka J . RAG1 core and V(D)J recombination signal sequences were derived from Transib transposons. PLoS Biol. 2005; 3(6):e181. PMC: 1131882. DOI: 10.1371/journal.pbio.0030181. View

12.

Rowe H, Trono D . Dynamic control of endogenous retroviruses during development. Virology. 2011; 411(2):273-87. DOI: 10.1016/j.virol.2010.12.007. View

13.

Gerdes P, Richardson S, Mager D, Faulkner G . Transposable elements in the mammalian embryo: pioneers surviving through stealth and service. Genome Biol. 2016; 17:100. PMC: 4862087. DOI: 10.1186/s13059-016-0965-5. View

14.

Shan B, Pan H, Najafov A, Yuan J . Necroptosis in development and diseases. Genes Dev. 2018; 32(5-6):327-340. PMC: 5900707. DOI: 10.1101/gad.312561.118. View

15.

Grootjans S, Vanden Berghe T, Vandenabeele P . Initiation and execution mechanisms of necroptosis: an overview. Cell Death Differ. 2017; 24(7):1184-1195. PMC: 5520172. DOI: 10.1038/cdd.2017.65. View

16.

Elsasser S, Noh K, Diaz N, Allis C, Banaszynski L . Histone H3.3 is required for endogenous retroviral element silencing in embryonic stem cells. Nature. 2015; 522(7555):240-244. PMC: 4509593. DOI: 10.1038/nature14345. View

17.

Boeke J, Garfinkel D, Styles C, Fink G . Ty elements transpose through an RNA intermediate. Cell. 1985; 40(3):491-500. DOI: 10.1016/0092-8674(85)90197-7. View

18.

Liu J, Gao M, He J, Wu K, Lin S, Jin L . The RNA mA reader YTHDC1 silences retrotransposons and guards ES cell identity. Nature. 2021; 591(7849):322-326. DOI: 10.1038/s41586-021-03313-9. View

19.

Stephenson H, Herzig A, Zychlinsky A . Beyond the grave: When is cell death critical for immunity to infection?. Curr Opin Immunol. 2015; 38:59-66. DOI: 10.1016/j.coi.2015.11.004. View

20.

He J, Fu X, Zhang M, He F, Li W, Abdul M . Transposable elements are regulated by context-specific patterns of chromatin marks in mouse embryonic stem cells. Nat Commun. 2019; 10(1):34. PMC: 6318327. DOI: 10.1038/s41467-018-08006-y. View