Tissue stiffening induces histone serotonylation and primes migratory cell states in vivo (ATAC-SEQ)

Here, we provide evidence for the involvement of a recently discovered chromatin marker, termed histone serotonylation, in the collective migration of cranial neural crest cells—an embryonic multipotent stem cell population. Our in vivo data revealed that histone serotonylation occurs in neural crest cells just before they start migrating and that its occurrence is essential for initiating the collective migration of these cells.

Surprisingly, we found that stiffening of the neural crest migratory substrate, the mesoderm, induces histone serotonylation by promoting the nuclear translocation of transglutaminase 2 (Tgm2), an enzyme that catalyzes the addition of serotonin to histones. Moreover, mechanical and molecular perturbations establish that shuttling of Tgm2 into the nucleus and concomitant increases in histone serotonylation are essential to trigger CCM in vivo.