GSE162605
ChIP-seq analysis of H3K9me3 signal from T-ALL cell line (Jurkat) upon fast CXCL12 stimulation
T-acute lymphoblastic leukaemia (T-ALL) is an aggressive haematological malignancy, which comprises the accumulation of malignant T-cell precursors. Despite current therapies, up to 20% of children with failure to respond to treatments and relapse. Our understanding of T-ALL infiltration and how leukaemia cells-microenvironment interactions play a role in the clinical outcome is still vague. In the present study, we showed a novel function of the chemokine CXCL12, which induced fast epigenetic changes within minutes in cell lines and primary T-ALL cells. Our results identified that CXCL12-mediated H3K9 methylation impacted on the global chromatin configuration and the nuclear mechanics of T-ALL cells. We characterised changes in the transcriptional profile of T-ALL cells associated with rapid CXCL12 stimulation. We demonstrated that cytoskeletal changes and protein kinase-C (PKC) activity were the molecular mechanisms by which CXCL12 promoted H3K9 methylation in T-ALL cells. Furthermore, targeting H3K9 methyltransferases reduced the migration and the nuclear deformability in both cell line and primary human ALL cells. Together, our data indicate a novel funcion of H3K9 methylation induced by CXCL12 in T-ALL cells, that reveals the significance of nuclear changes to mechanobiology and function of leukemia cells and emerges as a promising pharmacological target against T-ALL infiltration and dissemination. Overall design: Jurkat cells were culture in growth medium without  FBS (starving condition) for 90 min, then cells were stimulated or not with CXCL12 (100ng/ml) for 15 min. Cells were collected, and chromatin crosslinked with PFA. Cell lysates were anaysed for H3K9me3 ChIP-seq according to Active Motif protocol.