Distal Limb Patterning Requires Modulation of cis-Regulatory Activities by HOX13

Publication date: 13 December 2016
Source:Cell Reports, Volume 17, Issue 11
Author(s): Rushikesh Sheth, Iros Barozzi, David Langlais, Marco Osterwalder, Stephen Nemec, Hanqian L. Carlson, H. Scott Stadler, Axel Visel, Jacques Drouin, Marie Kmita
The combinatorial expression of Hox genes along the body axes is a major determinant of cell fate and plays a pivotal role in generating the animal body plan. Loss of HOXA13 and HOXD13 transcription factors (HOX13) leads to digit agenesis in mice, but how HOX13 proteins regulate transcriptional outcomes and confer identity to the distal-most limb cells has remained elusive. Here, we report on the genome-wide profiling of HOXA13 and HOXD13 in vivo binding and changes of the transcriptome and chromatin state in the transition from the early to the late-distal limb developmental program, as well as in Hoxa13^−/−; Hoxd13^−/− limbs. Our results show that proper termination of the early limb transcriptional program and activation of the late-distal limb program are coordinated by the dual action of HOX13 on cis-regulatory modules.

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Teaser

HOX13 homeobox transcription factors determine digit cell fate during limb bud development. Sheth et al. identify HOX13-dependent regulation of gene expression and chromatin state that suggests HOX13 activity at cis regulatory modules allows for a coordinated transition from the early to the late-distal program in the developing limb bud.


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