Hox binding specificity is directed by DNA sequence preferences and differential abilities to engage inaccessible chromatin [article]

Milica Bulajic, Divyanshi Srivastava, Jeremy Dasen, Hynek Wichterle, Shaun Mahony, Esteban O Mazzoni
2019 bioRxiv   pre-print
While Hox genes encode for conserved transcription factors (TFs), they are further divided into anterior, central, and posterior groups based on their DNA-binding domain similarity. The posterior group expanded in the deuterostome clade and patterns caudal and distal vertebrate structures such as the spinal neuronal diversity required for motor function. Our data revealed that limb-level patterning central Hoxc6, Hoxc8 and posterior Hoxc10 have a reduced ability to access occluded sites
more » ... luded sites compared to other tested Hox TFs. Thus, their genomic binding relies more on cell-specific chromatin accessibility. Although posterior Hoxc9, Hoxc10 and Hoxc13 induce different fates, they share motif preference. However, Hoxc9 and Hoxc13 have a unique ability to access sites occluded by chromatin, resulting in divergent genomic binding patterns. From these results, we propose that the differential abilities of posterior Hox TFs to bind to previously inaccessible chromatin is the predominant force driving their patterning diversification.
doi:10.1101/2019.12.29.890335 fatcat:27qhm7dgjzg2nk4oemvcnfu7fq