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

Cell Rep. 2016 Dec 13;17(11):2913-2926. doi: 10.1016/j.celrep.2016.11.039.

Abstract

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.

Keywords: ChIP-seq; HOX; Histone marks; Hoxa13; Hoxd13; chromatin state; digit; enhancer; limb development; transcriptional regulation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Body Patterning / genetics*
  • Chromatin / genetics
  • Extremities / growth & development*
  • Gene Expression Regulation, Developmental
  • Homeodomain Proteins / genetics*
  • Homeodomain Proteins / metabolism
  • Mice
  • Mice, Knockout
  • Protein Binding
  • Transcription Factors / genetics*
  • Transcription Factors / metabolism

Substances

  • Chromatin
  • Homeodomain Proteins
  • Hoxd13 protein, mouse
  • Transcription Factors
  • homeobox protein HOXA13