TY - JOUR
T1 - NF-κB signaling controls H3K9me3 levels at intronic LINE-1 and hematopoietic stem cell genes in cis
AU - Pelinski, Yanis
AU - Hidaoui, Donia
AU - Stolz, Anne
AU - Hermetet, François
AU - Chelbi, Rabie
AU - Diop, M’Boyba Khadija
AU - Chioukh, Amir M.
AU - Porteu, Françoise
AU - Elvira-Matelot, Emilie
N1 - Publisher Copyright:
© 2022 Pelinski et al.
PY - 2022/8/1
Y1 - 2022/8/1
N2 - 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.
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 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.
UR - http://www.scopus.com/inward/record.url?scp=85134426049&partnerID=8YFLogxK
U2 - 10.1084/jem.20211356
DO - 10.1084/jem.20211356
M3 - Article
C2 - 35802137
AN - SCOPUS:85134426049
SN - 0022-1007
VL - 219
JO - Journal of Experimental Medicine
JF - Journal of Experimental Medicine
IS - 8
M1 - e20211356
ER -