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Series GSE185766 Query DataSets for GSE185766
Status Public on Sep 29, 2022
Title Promoter repression and 3D-restructuring resolves divergent developmental gene expression in TADs [RNA-Seq]
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary Cohesin loop extrusion facilitates precise gene expression by continuously driving promoters to sample all enhancers located within the same topologically-associated domain (TAD). However, many TADs contain multiple genes with divergent expression patterns, thereby indicating additional forces further refine how enhancer activities are utilised. Here, we unravel the mechanisms enabling a new gene, Rex1, to emerge with divergent expression within the ancient Fat1 TAD in placental mammals. We show that such divergent expression is not determined by a strict enhancer-promoter compatibility code, intra-TAD position or nuclear envelope-attachment. Instead, TAD-restructuring in embryonic stem cells (ESCs) separates Rex1 and Fat1 with distinct proximal enhancers that independently drive their expression. By contrast, in later embryonic tissues, DNA methylation renders the inactive Rex1 promoter profoundly unresponsive to Fat1 enhancers within the intact TAD. Combined, these features adapted an ancient regulatory landscape during evolution to support two entirely independent Rex1 and Fat1 expression programs. Thus, rather than operating only as rigid blocks of co-regulated genes, TAD-regulatory landscapes can orchestrate complex divergent expression patterns in evolution.
 
Overall design We employed RNA-seq to map gene expression changes in mouse ESCs and and E11.5 limb buds harbouring large deletions surrounding the Rex1 and Fat1 genes.
 
Contributor(s) Robson MI, Ringel AR
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Submission date Oct 12, 2021
Last update date Oct 02, 2022
Contact name Michael I Robson
E-mail(s) robson@molgen.mpg.de
Organization name Max Planck Institute for Molecular Genetics
Street address Max Planck Institut für molekulare Genet, Ihnestrasse 63-73
City Berlin
ZIP/Postal code 14195
Country Germany
 
Platforms (2)
GPL21103 Illumina HiSeq 4000 (Mus musculus)
GPL24247 Illumina NovaSeq 6000 (Mus musculus)
Samples (41)
GSM5623342 RNA-seq__ESC_G4_wt_mouse_Rep-1
GSM5623343 RNA-seq__ESC_G4_wt_mouse_Rep-2
GSM5623344 RNA-seq__ESC_G4_wt_mouse_Rep-3
This SubSeries is part of SuperSeries:
GSE185775 Repression and 3D-restructuring resolves regulatory conflicts in evolutionarily rearranged genomes
Relations
BioProject PRJNA770714
SRA SRP341068

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Supplementary file Size Download File type/resource
GSE185766_RAW.tar 8.8 Gb (http)(custom) TAR (of BW)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file
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