Distinct Global Shifts in Genomic Binding Profiles of Limb Malformation Associated HOXD13 Mutations

ABSTRACT: We applied ChIP-seq to explore the effect of missense mutations in TFs on their genome wide binding profile. Using a retroviral expression system in chicken mesenchymal stem cells, we elucidated the mechanism underlying a novel missense mutation in HOXD13 (Q317K) associated with a complex hand and foot malformation phenotype. The glutamine at position 317 (position 50 of the homeodomain) is conserved in most homeodomains, a notable exception being bicoid-type homeodomains that have K at this position. Our results show that the mutation results in a shift in the binding profile of the mutant towards a bicoid/PITX1 motif. Gene expression analysis and functional assays using in vivo overexpression studies confirm that the mutation results in a partial conversion of HOXD13 into a TF with bicoi

ORGANISM(S): Gallus gallus

SUBMITTER: Peter Hansen 

PROVIDER: E-GEOD-44799 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress