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PITX1 Promotes Chondrogenesis and Myogenesis in Mouse Hindlimbs Through Conserved Regulatory Targets [RNA-Seq]

ABSTRACT: PITX1 Promotes Chondrogenesis and Myogenesis in Mouse Hindlimbs Through Conserved Regulatory Targets [RNA-Seq]

PROVIDER: PRJNA412667 | ENA |

REPOSITORIES: ENA

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PITX1 Promotes Chondrogenesis and Myogenesis in Mouse Hindlimbs Through Conserved Regulatory Targets [RNA-Seq]

Project description:The PITX1 transcription factor is expressed during hindlimb development, where it plays a critical role in directing hindlimb growth and the specification of hindlimb morphology. While it is known that PITX1 regulates hindlimb formation, in part, through activation of the Tbx4 gene, other transcriptional targets remain to be elucidated. We have used a combination of ChIP-seq and RNA-seq to investigate enhancer regions and target genes that are directly regulated by PITX1 in embryonic mouse hindlimbs. In addition, we have analyzed PITX1 binding sites in hindlimbs of Anolis lizards to identify ancient PITX1 regulatory targets. We find that PITX1-bound regions in both mouse and Anolis hindlimbs are strongly associated with genes implicated in limb and skeletal system development. Gene expression analyses reveal a large number of misexpressed genes in the hindlimbs of Pitx1-/- embryos. By intersecting misexpressed genes with genes that have neighboring mouse PITX1 binding sites, we identified 440 candidate targets of PITX1. Of these candidates, 68 exhibit ultra-conserved PITX1 binding events that are shared between mouse and Anolis hindlimbs. Among the ancient targets of PITX1 are important regulators of cartilage and skeletal muscle development, including Sox9 and Six1. Our data suggest that PITX1 promotes chondrogenesis and myogenesis in the hindlimb by direct regulation of several key members of the cartilage and muscle transcriptional networks.

2018-02-14 | GSE104459 | GEO

PITX1 Promotes Chondrogenesis and Myogenesis in Mouse Hindlimbs Through Conserved Regulatory Targets [ChIP-Seq]

2018-02-14 | GSE104457 | GEO

PITX1 Promotes Chondrogenesis and Myogenesis in Mouse Hindlimbs Through Conserved Regulatory Targets

Project description:PITX1 Promotes Chondrogenesis and Myogenesis in Mouse Hindlimbs Through Conserved Regulatory Targets

| PRJNA412664 | ENA

PITX1 Promotes Chondrogenesis and Myogenesis in Mouse Hindlimbs Through Conserved Regulatory Targets [ChIP-Seq]

Project description:PITX1 Promotes Chondrogenesis and Myogenesis in Mouse Hindlimbs Through Conserved Regulatory Targets [ChIP-Seq]

| PRJNA412663 | ENA

PITX1 promotes chondrogenesis and myogenesis in mouse hindlimbs through conserved regulatory targets.

Project description: Not available

| S-EPMC5785414 | biostudies-literature

PITX1 Promotes Chondrogenesis and Myogenesis in Mouse Hindlimbs Through Conserved Regulatory Targets

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

2018-02-14 | GSE104460 | GEO

Pitx1 broadly associates with limb enhancers and is enriched on hindlimb cis-regulatory elements

Project description:Extensive functional analyses have demonstrated that the pituitary homeodomain transcription factor Pitx1 plays a critical role in specifying hindlimb morphology in vertebrates. However, much less is known regarding the target genes and cis-regulatory elements through which Pitx1 acts. Earlier studies suggested that the hindlimb transcription factors Tbx4, HoxC10, and HoxC11 might be transcriptional targets of Pitx1, but definitive evidence for direct regulatory interactions has been lacking. Using ChIP-Seq on embryonic mouse hindlimbs, we have pinpointed the genome-wide location of Pitx1 binding sites during mouse hindlimb development and identified potential gene targets for Pitx1. We determined that Pitx1 binding is significantly enriched near genes involved in limb morphogenesis, including Tbx4, HoxC10, and HoxC11. Notably, Pitx1 is bound to the previously identified HLEA and HLEB hindlimb enhancers of the Tbx4 gene and to a newly identified Tbx2 hindlimb enhancer. Moreover, Pitx1 binding is significantly enriched on hindlimb relative to forelimb-specific cis-regulatory features that are differentially marked by H3K27ac. However, our analysis revealed that Pitx1 also strongly associates with many functionally verified limb enhancers that exhibit similar levels of activity in the embryonic mesenchyme of forelimbs and hindlimbs. We speculate that Pitx1 influences hindlimb morphology both through the activation of hindlimb specific enhancers as well as through the hindlimb-specific modulation of enhancers that are active in both sets of limbs. Embryonic hindlimb buds from 4 ICR mouse samples were used.

2012-12-01 | E-GEOD-41591 | biostudies-arrayexpress

Pitx1 broadly associates with limb enhancers and is enriched on hindlimb cis-regulatory elements

2012-12-01 | GSE41591 | GEO

Pitx1 directly controls the core limb development program to implement hindlimb identity [RNA-Seq]

Project description:Pitx1, critical regulator of a limited hindlimb-specific gene network, targets the limb development program common to both fore- and hindlimbs in order to implement hindlimb-specific limb morphology.

2017-09-19 | GSE100727 | GEO

Pitx1 directly controls the core limb development program to implement hindlimb identity [ChIP-Seq]

2017-09-19 | GSE100728 | GEO

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