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Series GSE252080 Query DataSets for GSE252080
Status Public on Dec 29, 2023
Title Synergistic insulation of regulatory domains by developmental genes and clusters of CTCF sites
Organism Mus musculus
Experiment type Other
Summary The specificity of gene expression during development requires the insulation of regulatory domains to avoid inappropriate enhancer-gene interactions. In vertebrates, this insulator function is mostly attributed to clusters of CTCF sites located at topologically associating domain (TAD) boundaries. However, TAD boundaries allow certain level of physical crosstalk across regulatory domains, which is at odds with the highly specific and precise expression of developmental genes. Here we show that developmental genes and nearby clusters of CTCF sites synergistically foster the robust insulation of regulatory domains. Firstly, we found that the TADs containing developmental genes have distinctive features, including the sequential organization of developmental genes and CTCF clusters near TAD boundaries. Most importantly, by genetically dissecting representative loci in mouse embryonic stem cells, we showed that developmental genes and CTCF sites synergistically strengthened the insulation capacity of nearby boundaries through different mechanisms. Namely, while CTCF sites prevent undesirable enhancer-gene contacts (i.e. physical insulation), developmental genes preferentially contribute to regulatory insulation through non-structural mechanisms involving promoter competition rather than enhancer blocking. Overall, our work provides important insights into the specificity of gene regulation, which in turn might help interpreting the pathological consequences of certain structural variants.
 
Overall design Capture-C experiments were performed to investigate enhancer-gene contacts within specific loci (i.e. Gbx2/Asb18 or Six3/Six2) in WT mouse embryonic stem cells (mESC) as well as in transgenic mESC lines containing different genomic re-arrangements (i.e. deletions or inversions). Where indicated the Capture-C experiments were performed upon differentiation of the mESC lines into anterior neural progenitors (NPC).
 
Contributor(s) Ealo T, Sanchez-Gaya V, Haro E, Rada-Iglesias A
Citation(s) 39179577
Submission date Dec 26, 2023
Last update date Sep 30, 2024
Contact name Alvaro Rada-Iglesias
E-mail(s) alvaro.rada@unican.es
Organization name Institute of Biomedicine and Biotechnology of Cantabria (IBBTEC), CSIC/University of Cantabria
Street address Albert Einstein 22, PCTCAN
City Santander
State/province Cantabria
ZIP/Postal code 39011
Country Spain
 
Platforms (1)
GPL24247 Illumina NovaSeq 6000 (Mus musculus)
Samples (40)
GSM7993392 WT_ESC_Gbx2SE_rep1
GSM7993393 WT_ESC_Gbx2SE_rep2
GSM7993394 WT_ESC_Asb18_rep1
Relations
BioProject PRJNA1057293

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE252080_71Kb_INV_ESC_Asb18.bw 83.7 Kb (ftp)(http) BW
GSE252080_71Kb_INV_ESC_Gbx2SE.bw 80.1 Kb (ftp)(http) BW
GSE252080_Del3XCTCF_71Kb_INV_ESC_Asb18.bw 89.5 Kb (ftp)(http) BW
GSE252080_Del3XCTCF_71Kb_INV_ESC_Gbx2SE.bw 90.9 Kb (ftp)(http) BW
GSE252080_Del3XCTCF_DelPromGbx2_ESC_Asb18.bw 84.5 Kb (ftp)(http) BW
GSE252080_Del3XCTCF_DelPromGbx2_ESC_Gbx2SE.bw 87.6 Kb (ftp)(http) BW
GSE252080_Del3XCTCF_ESC_Asb18.bw 90.2 Kb (ftp)(http) BW
GSE252080_Del3XCTCF_ESC_Gbx2SE.bw 85.0 Kb (ftp)(http) BW
GSE252080_Del6XCTCF_NPC_Six2.bw 80.8 Kb (ftp)(http) BW
GSE252080_Del6XCTCF_NPC_Six3SE.bw 78.3 Kb (ftp)(http) BW
GSE252080_Del6XCTCF_Six3KO_NPC_Six2.bw 82.0 Kb (ftp)(http) BW
GSE252080_Del6XCTCF_Six3KO_NPC_Six3SE.bw 80.4 Kb (ftp)(http) BW
GSE252080_DelPromGbx2_ESC_Asb18.bw 81.3 Kb (ftp)(http) BW
GSE252080_DelPromGbx2_ESC_Gbx2SE.bw 93.2 Kb (ftp)(http) BW
GSE252080_Six3KO_NPC_Six2.bw 74.3 Kb (ftp)(http) BW
GSE252080_Six3KO_NPC_Six3SE.bw 79.9 Kb (ftp)(http) BW
GSE252080_WT_ESC_Asb18.bw 91.1 Kb (ftp)(http) BW
GSE252080_WT_ESC_Gbx2SE.bw 89.3 Kb (ftp)(http) BW
GSE252080_WT_NPC_Six2.bw 82.3 Kb (ftp)(http) BW
GSE252080_WT_NPC_Six3SE.bw 80.3 Kb (ftp)(http) BW
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