Transcriptomics,Genomics

Dataset Information

163

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


ABSTRACT: 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. Overall design: Totla mRNAs from dissected distal parts of e11.5 forelimb, of wild-type as well as Hoxa13-/-;Hoxd13-/- mice

INSTRUMENT(S): Illumina HiSeq 2000 (Mus musculus)

SUBMITTER: Rushikesh Sheth 

PROVIDER: GSE81357 | GEO | 2016-12-14

SECONDARY ACCESSION(S): PRJNA321344

REPOSITORIES: GEO

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Publications

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

Sheth Rushikesh R   Barozzi Iros I   Langlais David D   Osterwalder Marco M   Nemec Stephen S   Carlson Hanqian L HL   Stadler H Scott HS   Visel Axel A   Drouin Jacques J   Kmita Marie M  

Cell reports 20161201 11


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 chro  ...[more]

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