| Autor: |
Yanis Pelinski, Donia Hidaoui, Anne Stolz, François Hermetet, Rabie Chelbi, M’boyba Khadija Diop, Amir M. Chioukh, Françoise Porteu, Emilie Elvira-Matelot |
| Rok vydání: |
2021 |
| Předmět: |
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| Popis: |
SUMMARYIonizing 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 contribute 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 before IR 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 of HSCs while allowing expression of immune genes during myeloid regeneration or damage-induced bone marrow ablation. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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