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Title: Repression of endogenous retroviruses prevents antiviral immune response and is required for mammary gland development
Author: Avgustinova, Alexandra
Laudanna, Carmelo
Pascual García, Mónica
Rovira, Quirze
Djurec, Magdolna
Castellanos, Andrés
Urdiroz Urricelqui, Uxue
Marchese, Domenica
Prats, Neus
Van Keymeulen, Alexandra
Heyn, Holger
Vaquerizas, Juan M.
Aznar Benitah, Salvador
Keywords: Retrovirus
Glàndules mamàries
Mammary glands
Issue Date: 18-May-2021
Publisher: Elsevier
Abstract: The role of heterochromatin in cell fate specification during development is unclear. We demonstrate that loss of the lysine 9 of histone H3 (H3K9) methyltransferase G9a in the mammary epithelium results in de novo chromatin opening, aberrant formation of the mammary ductal tree, impaired stem cell potential, disrupted intraductal polarity, and loss of tissue function. G9a loss derepresses long terminal repeat (LTR) retroviral sequences (predominantly the ERVK family). Transcriptionally activated endogenous retroviruses generate double-stranded DNA (dsDNA) that triggers an antiviral innate immune response, and knockdown of the cytosolic dsDNA sensor Aim2 in G9a knockout (G9acKO) mammary epithelium rescues mammary ductal invasion. Mammary stem cell transplantation into immunocompromised or G9acKO-conditioned hosts shows partial dependence of the G9acKO mammary morphological defects on the inflammatory milieu of the host mammary fat pad. Thus, altering the chromatin accessibility of retroviral elements disrupts mammary gland development and stem cell activity through both cell-autonomous and non-autonomous mechanisms.
Note: Versió postprint del document publicat a:
It is part of: Cell Stem Cell, 2021
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Appears in Collections:Articles publicats en revistes (Institut de Recerca Biomèdica (IRB Barcelona))

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