A role for HOX13 proteins in the regulatory switch between TADs at the HoxD locus.

ABSTRACT: During vertebrate limb development, Hoxd genes are regulated following a bimodal strategy involving two topologically associating domains (TADs) located on either side of the gene cluster. These regulatory landscapes alternatively control different subsets of Hoxd targets, first into the arm and subsequently into the digits. We studied the transition between these two global regulations, a switch that correlates with the positioning of the wrist, which articulates these two main limb segments. We show that the HOX13 proteins themselves help switch off the telomeric TAD, likely through a global repressive mechanism. At the same time, they directly interact with distal enhancers to sustain the activity of the centromeric TAD, thus explaining both the sequential and exclusive operating proces

SUBMITTER: Beccari L 

PROVIDER: S-EPMC4888838 | biostudies-literature | 2016 May

REPOSITORIES: biostudies-literature