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HOX13 activity reprograms cis-regulatory modules during digit development

ABSTRACT: HOX13 activity reprograms cis-regulatory modules during digit development

PROVIDER: PRJNA321343 | ENA |

REPOSITORIES: ENA

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HOX13 activity reprograms cis-regulatory modules during digit development (RNA-Seq)

Project description:The combinatorial expression of the Hox genes along the body axes, referred to as the HOX code, is a major determinant of cell fate and plays a prevailing role in generating the animal body plan. In developing limb buds, the paralogous group 13 genes of the HoxA and HoxD clusters are essential for patterning the distal-most limb structures, the digits. Inactivation of HOXA13 and HOXD13 transcription factors (HOX13) leads to complete digit agenesis in mice, but how HOX13 regulate transcriptional outcomes and confer identity to the distal-most limb cells has remained elusive. Here we performed genome-wide profiling of HOX13 by chromatin immunoprecipitation and analyzed the transcriptome and chromatin state of wild type early and late-distal limb buds, as well as Hoxa13-/-;Hoxd13-/- compound mutant limb buds. Our results show that inactivation of HOX13 impairs the activation and repression of putative cis-regulatory modules specific to the late-distal limb cells. Loss of HOX13 also disrupts the specific, spatial patterning of gene expression along the proximal-distal axis of the developing limb buds. These 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.

2016-12-14 | GSE81357 | GEO

HOX13 activity reprograms cis-regulatory modules during digit development (ChIP-Seq)

2016-12-14 | GSE81356 | GEO

HOX13 activity reprograms cis-regulatory modules during digit development

Project description:This SuperSeries is composed of the SubSeries listed below.

2016-12-14 | GSE81358 | GEO

HOX13-dependent chromatin accessibility underlies the transition towards the digit development program[ChIP-seq]

Project description:Pioneer factors are transcription factors able to recognize their target site even concealed in “closed” chromatin, eventually eliciting the switch to accessible targets for other transcription factors and the transcriptional machinery. As such, pioneer factors play a key role in switching cell fate. Here, we provide evidence that HOXA13 and HOXD13 (HOX13 hereafter), two transcription factors of the Hox family of developmental genes, act as pioneer factors in the developing limb. We show that Hox13 function is mandatory for switching a series of target loci to an accessible chromatin state, allowing the binding of other transcription factors. These target loci include an enhancer previously identified as essential for the pentadactyl state, providing evidence that the pioneer activity of HOX13 is key for digit patterning. Based on the data reported here and previous studies, we propose that, during the fin-to-limb transition, the implementation of digit-specific enhancer elements had required an ancestral pioneer function of the HOX13 TFs.

2020-03-25 | GSE123480 | GEO

HOX13-dependent chromatin accessibility underlies the transition towards the digit development program[ATAC-Seq]

2020-04-03 | GSE123481 | GEO

Mus musculus

Project description:HOX13 activity reprograms cis-regulatory modules during digit development (RNA-Seq)

| PRJNA321344 | ENA

Mus musculus

Project description:HOX13 activity reprograms cis-regulatory modules during digit development (ChIP-Seq)

| PRJNA321345 | ENA

HOX13-dependent chromatin accessibility underlies the transition towards the digit development program

Project description:HOX13-dependent chromatin accessibility underlies the transition towards the digit development program

| PRJNA508886 | ENA