Tissue stiffening induces histone serotonylation and primes migratory cell states in vivo [RNA-seq]

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

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