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PITX1 promotes chondrogenesis and myogenesis in mouse hindlimbs through conserved regulatory targets
- Source :
- Developmental Biology. 434:186-195
- Publication Year :
- 2018
- Publisher :
- Elsevier BV, 2018.
-
Abstract
- 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−/− mouse 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.
- Subjects :
- 0301 basic medicine
animal structures
Transcription, Genetic
Reptilian Proteins
SOX9
Hindlimb
Biology
Muscle Development
Article
Mice
03 medical and health sciences
Gene expression
Animals
Paired Box Transcription Factors
Enhancer
Molecular Biology
Transcription factor
Gene
Homeodomain Proteins
Mice, Knockout
Mice, Inbred ICR
Myogenesis
Lizards
SOX9 Transcription Factor
Cell Biology
Chondrogenesis
Cell biology
030104 developmental biology
Developmental Biology
Subjects
Details
- ISSN :
- 00121606
- Volume :
- 434
- Database :
- OpenAIRE
- Journal :
- Developmental Biology
- Accession number :
- edsair.doi.dedup.....b50ed33621a604eef84cdfee84eca1b4
- Full Text :
- https://doi.org/10.1016/j.ydbio.2017.12.013