HOX13-dependent chromatin accessibility underlies the transition towards the digit development program[ChIP-seq]

Pioneer factors are transcription factors able to recognize their target site even concealed in “closed” chromatin, eventually eliciting the switch to accessible targets for other transcription factors and the transcriptional machinery. As such, pioneer factors play a key role in switching cell fate. Here, we provide evidence that HOXA13 and HOXD13 (HOX13 hereafter), two transcription factors of the Hox family of developmental genes, act as pioneer factors in the developing limb. We show that Hox13 function is mandatory for switching a series of target loci to an accessible chromatin state, allowing the binding of other transcription factors. These target loci include an enhancer previously identified as essential for the pentadactyl state, providing evidence that the pioneer activity of HOX13 is key for digit patterning. Based on the data reported here and previous studies, we propose that, during the fin-to-limb transition, the implementation of digit-specific enhancer elements had required an ancestral pioneer function of the HOX13 TFs. ChIP-seq: e11.5 mouse forelimb WT HOXA11, e11.5 mouse forelimb RA11KI HOXA11.