PT  - JOURNAL ARTICLE
AU  - Yanis Pelinski
AU  - Donia Hidaoui
AU  - Anne Stolz
AU  - François Hermetet
AU  - Rabie Chelbi
AU  - M’boyba Khadija Diop
AU  - Amir M. Chioukh
AU  - Françoise Porteu
AU  - Emilie Elvira-Matelot
TI  - The NF-κB pathway controls H3K9me3 levels at intronic LINE-1 elements and hematopoietic stem cell gene expression in cis
AID  - 10.1101/2021.06.08.447574
DP  - 2022 Jan 01
TA  - bioRxiv
PG  - 2021.06.08.447574
4099  - http://biorxiv.org/content/early/2022/01/06/2021.06.08.447574.short
4100  - http://biorxiv.org/content/early/2022/01/06/2021.06.08.447574.full
AB  - 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 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.Competing Interest StatementThe authors have declared no competing interest.