Transcriptomics,Genomics

Dataset Information

159

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 processes of these two regulatory domains. We propose a model whereby the activation of Hox13 gene expression in distal limb cells both interrupts the proximal Hox gene regulation and re-enforces the distal regulation. In the absence of HOX13 proteins, a proximal limb structure grows without any sign of wrist articulation, likely related to an ancestral fish-like condition. Overall design: RNA-seq analysis of proximal and distal forelimbs from E12.5 wt or Hoxa13-/-;Hoxd13-/- mutant embryos

INSTRUMENT(S): Illumina HiSeq 2500 (Mus musculus)

SUBMITTER: Nayuta Yakushiji-Kaminatsui  

PROVIDER: GSE79260 | GEO | 2016-05-19

SECONDARY ACCESSION(S): PRJNA315297

REPOSITORIES: GEO

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Publications


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. W  ...[more]

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