Diversification of posterior Hox patterning by graded ability to engage inaccessible chromatin [ChIP-seq]

While Hox genes encode for similar transcription factors (TFs), they induce different fates across body axes. We sought to understand how Hox TF genomic binding preferences relate to their patterning activities during neuronal differentiation. To generate the required neuronal diversity for locomotor activity, Hox TFs specify spinal motor neuron and interneuron subtypes along the rostro-caudal axis. Our data revelated that Hoxc6 and Hoxc8 of the central group induce limb-innervating fates by binding to the same sites. On the other hand, the posterior group Hox genes assign different positional identities: Hoxc9 (thoracic), Hoxc10 (limb-innervating) and Hox13 (axial elongation termination) by binding to distinct sites with the same primary motif. We find that their genomic binding distributions are explained by differential abilities to bind to previously inaccessible chromatin. Thus, the vertebrate posterior Hox expansion and its associated patterning diversification is the product of their differential abilities to associate with less accessible chromatin. Overall design: ChIP-Seq was used to characterize Hox TF binding during ESC-to-MN differentiation