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Series GSE262006 Query DataSets for GSE262006
Status Public on Mar 22, 2024
Title Temporal constraints on enhancer usage shape the regulation of limb gene transcription
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Genome binding/occupancy profiling by high throughput sequencing
Summary Repertoires of transcriptional enhancers orchestrate gene expression during embryonic development, thereby shaping the forms and functions of organs. Within these repertoires individual enhancers display spatially distinct or overlapping activities that collectively build up the expression domain of cognate genes. However, the temporal specificity of these enhancers - how their activities change over developmental time to dynamically influence gene expression - remains uncharacterized. Here, we observed that temporally restricted enhancer repertoires are embedded at numerous loci associated with mouse limb development. To monitor how such enhancer repertoires govern gene transcription in vivo across extensive developmental periods, we introduce the regulatory trajectory framework. This paradigm conceptually involves transcriptional initiation, marking the beginning of gene expression, followed by its maintenance over time, and ultimately decommissioning, leading to gene repression. To track and sort cells undergoing these distinct phases, we devised a transgenic recorder approach at the Shox2 model locus. Through this method, we discovered that cells maintaining Shox2 transcription in early and late limb development relies on distinct, temporally restricted enhancer repertoires. We demonstrate that eliminating early- or late-acting enhancers only transiently affects Shox2 expression indicating that these enhancer repertoires function independently. Additionally, we found that changes in the 3D topology of the locus associate with enhancer activities and that a rapid loss of enhancer-promoter contacts occurs during decommissioning. Finally, we show that the decommissioning of the Shox2 locus can be actively driven by Hoxd13, a gene which expression is known to antagonize Shox2. Overall, our work uncovers the dependency of developmental genes on enhancers with temporally restricted activities to generate complex expression patterns over time and shed light on the dynamics of enhancer-promoter interactions.
Overall design Refer to individual Series
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Submission date Mar 20, 2024
Last update date Mar 23, 2024
Contact name Guillaume Andrey
Phone +41223795703
Organization name University of Geneva
Department Department of Genetic Medicine and Development
Street address Rue Michel-Servet 1
City Geneva
ZIP/Postal code 1211
Country Switzerland
Platforms (2)
GPL21103 Illumina HiSeq 4000 (Mus musculus)
GPL24247 Illumina NovaSeq 6000 (Mus musculus)
Samples (123)
GSM8155794 scMm_Shox2trac_HL_E105_rep1
GSM8155795 scMm_Shox2trac_HL_E105_rep2
GSM8155796 scMm_Shox2trac_HL_E115_rep1
This SuperSeries is composed of the following SubSeries:
GSE262002 Temporal constraints on enhancer usage shape the regulation of limb gene transcription
GSE262003 Temporal constraints on enhancer usage shape the regulation of limb gene transcription
GSE262004 Temporal constraints on enhancer usage shape the regulation of limb gene transcription
BioProject PRJNA1090013

Download family Format
SOFT formatted family file(s) SOFTHelp
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Supplementary file Size Download File type/resource
GSE262006_RAW.tar 12.9 Gb (http)(custom) TAR (of BROADPEAK, BW, H5, TXT)
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