NF-κB signaling controls H3K9me3 levels at intronic LINE-1 and hematopoietic stem cell genes in cis

Yanis Pelinski, Donia Hidaoui, Anne Stolz, François Hermetet, Rabie Chelbi, M’Boyba Khadija Diop, Amir M. Chioukh, Françoise Porteu, Emilie Elvira-Matelot

    Résultats de recherche: Contribution à un journalArticleRevue par des pairs

    6 Citations (Scopus)

    Résumé

    Ionizing radiations (IR) alter hematopoietic stem cell (HSC) function on the long term, but the mechanisms underlying these effects are still poorly understood. We recently showed that IR induces the derepression of L1Md, the mouse young subfamilies of LINE-1/L1 retroelements. L1 contributes to gene regulatory networks. However, how L1Md are derepressed and impact HSC gene expression are not known. Here, we show that IR triggers genome-wide H3K9me3 decrease that occurs mainly at L1Md. Loss of H3K9me3 at intronic L1Md harboring NF-κB binding sites motifs but not at promoters is associated with the repression of HSC-specific genes. This is correlated with reduced NFKB1 repressor expression. TNF-α treatment rescued all these effects and prevented IR-induced HSC loss of function in vivo. This TNF-α/NF-κB/H3K9me3/L1Md axis might be important to maintain HSCs while allowing expression of immune genes during myeloid regeneration or damage-induced bone marrow ablation.

    langue originaleAnglais
    Numéro d'articlee20211356
    journalJournal of Experimental Medicine
    Volume219
    Numéro de publication8
    Les DOIs
    étatPublié - 1 août 2022

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