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Repression of endogenous retroviruses is required for mammary gland development and homeostasis [microarray]

ABSTRACT: Repression of endogenous retroviruses is required for mammary gland development and homeostasis [microarray]

PROVIDER: PRJNA713294 | ENA |

REPOSITORIES: ENA

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Repression of endogenous retroviruses is required for mammary gland development and homeostasis [microarray]

Project description:We demonstrate that loss of the histone H3K9 methyltransferase G9a in the developing mammary epithelium results in de novo chromatin opening which leads to severely impaired development of the mammary ductal tree, concomitant with impaired stem cell potential and disrupted intraductal polarity. Intriguingly, these phenotypes are not attributed to alterations in lineage specification and fidelity of the basal and luminal cell fates. Instead, increased chromatin opening in G9a-ablated mammary epithelium results in derepression of Long Terminal Repeat (LTR) sequences, most prominently of the ERVK family. When reverse-transcribed, these endogenous retroviruses generate double-stranded DNA (dsDNA) that accumulates in the cytosol of G9acKO mammary epithelial cells and trigger a pyroptotic antiviral innate immune response within mammary fat pads. Importantly, this altered G9acKO mammary milieu precludes functional outgrowth of even wild-type mammary stem cells upon transplantation. Our results show that tight repression of endogenous retroviruses is required for proper mammary gland development and maintenance. We demonstrate that altering chromatin accessibility of retroviral elements, as occurs during aging and cancer, severely disrupts functional mammary gland development and mammary stem cell activity through both cell autonomous and cell non-autonomous mechanisms.

2021-05-18 | GSE168624 | GEO

Repression of endogenous retroviruses is required for mammary gland development and homeostasis

Project description:Repression of endogenous retroviruses is required for mammary gland development and homeostasis

| PRJNA630715 | ENA

Repression of endogenous retroviruses is required for mammary gland development and homeostasis [scRNA-Seq]

2021-05-18 | GSE149953 | GEO

Repression of endogenous retroviruses is required for mammary gland development and homeostasis [ATAC-Seq]

2021-05-18 | GSE149977 | GEO

Repression of endogenous retroviruses is required for mammary gland development and homeostasis [RNA-Seq]

2021-05-18 | GSE149976 | GEO

Repression of endogenous retroviruses is required for mammary gland development and homeostasis [RNA-Seq]

Project description:Repression of endogenous retroviruses is required for mammary gland development and homeostasis [RNA-Seq]

| PRJNA630719 | ENA

Repression of endogenous retroviruses is required for mammary gland development and homeostasis [ATAC-Seq]

Project description:Repression of endogenous retroviruses is required for mammary gland development and homeostasis [ATAC-Seq]

| PRJNA630717 | ENA

Repression of endogenous retroviruses is required for mammary gland development and homeostasis [scRNA-Seq]

Project description:Repression of endogenous retroviruses is required for mammary gland development and homeostasis [scRNA-Seq]

| PRJNA630720 | ENA

Co-option of endogenous retroviruses through genetic escape from TRIM28 repression

Project description:Co-option of endogenous retroviruses through genetic escape from TRIM28 repression

| PRJNA854089 | ENA

Co-option of endogenous retroviruses through genetic escape from TRIM28 repression

Project description:Endogenous retroviruses (ERVs) have rewired host gene networks. To explore the origins of co-option, we employed an active murine ERV, IAPEz, and an embryonic stem cell (ESC) to neural progenitor cell (NPC) differentiation model. Epigenetic silencing via TRIM28 maps to a 190bp sequence encoding the IAP signal peptide, which confers retrotransposition activity. A subset of ‘escapee’ IAPs (~15%) exhibit significant genetic divergence from this sequence. Canonical repressed IAPs succumb to a previously undocumented demarcation by H3K9me3 and H3K27me3 in NPCs. Escapee IAPs, in contrast, evade epigenetic repression in both cell types, resulting in their transcriptional derepression, particularly in NPCs. We validate the enhancer function of a 47bp sequence within the U3 region of the LTR and show that escapee IAPs convey an activating effect on nearby neural genes. In sum, co-opted ERVs stem from genetic escapees that have lost vital sequences required for both TRIM28 restriction and autonomous retrotransposition.

2023-05-10 | GSE207184 | GEO

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