Mus musculus
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ABSTRACT:
PROVIDER: PRJNA321344 | ENA |
REPOSITORIES: ENA
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Project description:HOX13 activity reprograms cis-regulatory modules during digit development
| PRJNA321343 | ENA
Project description:HOX13 activity reprograms cis-regulatory modules during digit development (ChIP-Seq)
| PRJNA321345 | ENA
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
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 | GSE81356 | GEO
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
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.
2020-04-03 | GSE123481 | GEO
Project description:Lmx1b is a homeodomain transcription factor responsible for limb dorsalization. Despite striking double-ventral (loss-of-function) and double-dorsal (gain-of-function) limb phenotypes, no direct downstream gene targets in the limb have been confirmed. To determine direct targets of Lmx1b during limb dorsalization (E12.5), we performed chromatin immunoprecipitation followed by next generation sequencing (ChIP-seq). Nearly 84% (n=617) of the Lmx1b-bound genomic fragments or intervals (LBIs) identified by two Lmx1b-ChIP-seqs overlap with chromatin regulatory marks indicative of potential cis-regulatory modules (PCRMs). In addition, 73 LBIs mapped to known cis-regulatory modules (CRMs) active during limb development. We compared Lmx1b-bound PCRMs to genes differentially expressed by Lmx1b at E12.5 and found 292 PCRMs within 1 Mb of 254 Lmx1b-regulated genes. Gene ontology analysis of these associated genes suggests that Lmx1b mediates dorsalization through the regulation of extracellular matrix production, bone/joint formation, axonal guidance, vascular development, cell proliferation and cell movement. We validated the functional activity of 2 PCRMs associated to Lmx1b-regulated genes, demonstrating activity and overlap with the associated gene during limb development. This is the first report to describe the genome-wide distribution of Lmx1b binding during limb development, directly linking Lmx1b to targets that accomplish limb dorsalization.
2017-05-06 | GSE84064 | GEO
Project description:HOX13-dependent chromatin accessibility underlies the transition towards the digit development program
| PRJNA508886 | ENA
Project description:Genotyping 323 Europeans in order to perform cis-eQTL analysis in 9 tissue cell types. Identification of regulatory modules across genes and tissues on the basis of correlated SNPs in expression associated patterns. Integration of cis-eQTLs regulatory modules with known 200 IBD loci.
2018-04-28 | E-MTAB-6666 | biostudies-arrayexpress