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Mus musculus
24 Downloadable Samples
Illumina HiSeq 2500
Description
Despite decades of interest, the mechanisms that control Hox gene expression are not yet fully understood. It was recently proposed that Hotair, a lncRNA transcribed from the HoxC cluster, regulates HoxD gene expression via Polycomb targeting and thus is important for correct skeletal development. However, genetic manipulations of the locus led to conflicting results regarding the roles of Hotair. Here, we analyze the molecular and phenotypic consequences of deleting the Hotair locus in vivo. In contradiction with previous findings, we show that deleting Hotair has no detectable effect on HoxD gene expression in vivo. We could not observe any morphological alteration in mice lacking the Hotair locus. However, we find a significant impact of deleting Hotair on the expression of neighboring genes Hoxc11 and Hoxc12. Our results do not support an RNA-dependent role for Hotair in vivo, but argue in favor of a DNA-dependent effect of Hotair deletion on the transcriptional landscape in cis. Overall design: We micro-dissected wild type and Del(Hotair)-/- E12.5 embryos into 6 segments: forelimbs (FL), hindlimbs (HL), genital tubercle (GT), trunk section corresponding to the lumbar/sacral region (T1); trunk section corresponding to the sacral/caudal region (T2) and trunk section corresponding to the caudal region (T3). We generated strand-specific RNA-seq data for each segment, in two biological replicates and we performed differential expression analyses for each tissue. Furthermore, we analyzed the impact of deleting the Hotair locus on the local transcriptional landscape, in the HoxC cluster.
Publication Title
Hotair Is Dispensible for Mouse Development.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 4 Downloadable Samples
- Illumina HiSeq 2500
Description
In this work we have analyzed the transcriptomic profiles of E9 mouse embryos. We show that Hoxd1 and Haglr transcripts are absent after targeted deletion of the CpG: 114 island. Overall design: RNA-seq analysis of trunk from the anterior limit of the forelimb bud to the tailbud, aiming to exclude all extra-embryonic, head, cervical and heart tissues. Individuals 443 (wt) and 445 (Del(CpG114) homozygous), were siblings from the same dam, while biological replicates 456 (wt) and 455 (Del(CpG114) homozygous) were siblings from another dam.
Publication Title
Control of growth and gut maturation by <i>HoxD</i> genes and the associated lncRNA <i>Haglr</i>.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 2 Downloadable Samples
- Illumina HiSeq 2500
Description
Hox genes are required during the morphogenesis of both vertebrate digits and external genitals.We investigated whether transcription in such distinct contexts involves a shared enhancer-containing landscape. We show that the same regulatory topology is used, yet with some tissue-specific enhancer-promoter interactions, suggesting the hijacking of a regulatory backbone from one context to the other. In addition, comparable organizations are observed at both HoxA and HoxD clusters, which separated through genome duplication in an ancestral invertebrate animal.We propose that this convergent regulatory evolution was triggered by the pre-existence of some chromatin architecture, thus facilitating the subsequent recruitment of the appropriate transcription factors. Such regulatory topologies may have both favored and constrained the evolution of pleiotropic developmental loci in vertebrates. Overall design: RNA-seq from mouse E12.5 digits cells and mouse E15.5 genital tubercle cells.
Publication Title
Convergent evolution of complex regulatory landscapes and pleiotropy at Hox loci.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 6 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The spatial and temporal control of Hox gene transcription is essential for patterning the vertebrate body axis. Although this process involves changes in histone posttranslational modifications, the existence of particular three-dimensional (3D) architectures remained to be assessed in vivo. Using high-resolution chromatin conformation capture methodology, we examined the spatial configuration of Hox clusters in embryonic mouse tissues where different Hox genes are active. When the cluster is transcriptionally inactive, Hox genes associate into a single 3D structure delimited from flanking regions. Once transcription starts, Hox clusters switch to a bimodal 3D organization where newly activated genes progressively cluster into a transcriptionally active compartment. This transition in spatial configurations coincides with the dynamics of chromatin marks, which label the progression of the gene clusters from a negative to a positive transcription status. This spatial compartmentalization may be key to process the collinear activation of these compact gene clusters.
Publication Title
The dynamic architecture of Hox gene clusters.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Illumina HiSeq 2000
Description
Hox genes are required for the development of the intestinal caecum, a major organ of species eating plants. We have analysed the transcriptional regulation of Hoxd genes in caecal buds and show that they are controlled by a series of enhancers located in a gene desert telomeric to the HoxD cluster. The start site of two neighboring and opposite long non-coding RNAs, Hotdog and Twin of Hotdog, specifically transcribed in the caecum, contacts the expressed Hoxd genes in the framework of a topological domain, a large domain of interactions, which ensures a robust transcription of these genes during caecum budding. We show that hedgehogs have kept this regulatory potential despite the absence of caecum, suggesting that these enhancers are used in other developmental situations. In this context, we discuss some striking similarities between the caecum and the limb buds, suggesting the implementation of a common budding tool-kit. Overall design: Transcriptional activity at the HoxD locus in the murine developing gut at E13, Differential gene expression analysis along the murine developing gut
Publication Title
Multiple enhancers regulate Hoxd genes and the Hotdog LncRNA during cecum budding.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples
SRP018708- Mus musculus
- 1 Downloadable Sample
- Illumina Genome Analyzer II
Description
Hox genes are required for the development of the intestinal caecum, a major organ of species eating plants. We have analysed the transcriptional regulation of Hoxd genes in caecal buds and show that they are controlled by a series of enhancers located in a gene desert telomeric to the HoxD cluster. The start site of two neighboring and opposite long non-coding RNAs, Hotdog and Twin of Hotdog, specifically transcribed in the caecum, contacts the expressed Hoxd genes in the framework of a topological domain, a large domain of interactions, which ensures a robust transcription of these genes during caecum budding. We show that hedgehogs have kept this regulatory potential despite the absence of caecum, suggesting that these enhancers are used in other developmental situations. In this context, we discuss some striking similarities between the caecum and the limb buds, suggesting the implementation of a common budding tool-kit. Transcriptional activity at the HoxD locus in developing caeca at E13.5 Overall design: Transcriptional activity at the HoxD locus in developing caeca at E13.5
Publication Title
Multiple enhancers regulate Hoxd genes and the Hotdog LncRNA during cecum budding.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 1 Downloadable Sample
- Illumina HiSeq 2500
Description
Analysis of gene expression in the distal forelimbs Overall design: RNA-Seq polyA on transcripts extracted from the dissection of three pairs of embryonnic forelimbs at E12.5
Publication Title
Nanoscale spatial organization of the HoxD gene cluster in distinct transcriptional states.
Sample Metadata Fields
Cell line, Subject
View Samples- Mus musculus
- 4 Downloadable Samples
- Illumina HiSeq 2500
Description
During vertebrate limb development, Hoxd genes are regulated following a bimodal strategy involving two topologically associating domains (TADs) located on either side of the gene cluster. These regulatory landscapes alternatively control different subsets of Hoxd targets, first into the arm and, subsequently, into the digits. We studied the transition between these two global regulations, a switch that correlates with the positioning of the wrist, which articulates these two main limb segments. We show that the HOX13 proteins themselves help switch off the telomeric TAD, likely through a global repressive mechanism. At the same time, they directly interact with distal enhancers to sustain the activity of the centromeric TAD, thus explaining both the sequential and exclusive operating processes of these two regulatory domains. We propose a model whereby the activation of Hox13 gene expression in distal limb cells both interrupts the proximal Hox gene regulation and re-enforces the distal regulation. In the absence of HOX13 proteins, a proximal limb structure grows without any sign of wrist articulation, likely related to an ancestral fish-like condition. Overall design: RNA-seq analysis of proximal and distal forelimbs from E12.5 wt or Hoxa13-/-;Hoxd13-/- mutant embryos
Publication Title
A role for HOX13 proteins in the regulatory switch between TADs at the HoxD locus.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 6 Downloadable Samples
- Illumina HiSeq 2500
Description
In this work we have analyzed the transcriptomic profiles of E13.5 mouse embryonic mammary buds. We show that Hoxd8 and Hoxd9, two gene members of the HoxD cluster, are transcribed during mammary bud development. Yet, unlike in other developmental contexts, their co-expression does not rely upon the same regulatory mechanism. Hoxd8 is regulated by the combined activity of closely located sequences and the most distant telomeric gene desert. On the other hand, Hoxd9 is controlled by an enhancer sequence also located within the telomeric gene desert, but which has no impact on Hoxd8 transcription, thus constituting an exception to the global regulations systematically observed at this locus. The latter DNA region is also involved in Hoxd gene regulation in other contexts and strongly interacts with Hoxd9 in all tissues analyzed so far as well as in other vertebrate species, indicating that its regulatory activity was already operational before the appearance of mammary glands. Within this DNA region and neighboring the CS39 limb enhancer, we further identified a short sequence conserved in therian mammals and capable of enhancer activity in the mammary buds. We propose that Hoxd gene regulation in embryonic mammary buds evolved by hijacking a preexisting regulatory landscape, which was already at work before the emergence of mammals in structures such like the limbs or the intestinal tract. Overall design: RNA-seq analysis of e13.5 mammary buds and adjacent embryonic skin
Publication Title
Control of Hoxd gene transcription in the mammary bud by hijacking a preexisting regulatory landscape.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 31 Downloadable Samples
- Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
The nuclear bile acid receptor FXR is a PKA- and FOXA2-sensitive activator of fasting hepatic gluconeogenesis.
Sample Metadata Fields
Sex, Specimen part, Treatment
View Samples