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Series GSE178838 Query DataSets for GSE178838
Status Public on Jan 21, 2022
Title GLI transcriptional repression is inert prior to HH pathway activation
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Genome binding/occupancy profiling by high throughput sequencing
Summary Purpose: Most Hedgehog responsive gene expression is mediated through GLI de-repression. Additionally GLI -repression is proposed to play roles in limb pre-patterning before HH pathway activation. This study evaluates if GLI repression is established prior to HH pathway activation.
Methods: To determine if GLI-repression is established prior to pathway activation, we used genomic approaches to study GLI-mediated repression using the mouse developing limb as a model. We identified pre-HH (E9.25, 21-23S) and post-HH (E10.5, 32-25S) GLI3 binding regions using CUT&RUN for endogenous FLAG-tagged GLI3 proteins. Using a combination of ChIP-seq, CUT&RUN, CUT&Tag, ATAC-seq and RNA-seq, we tested whether loss of Gli3 prior to HH signaling was able to de-repress genes and enhancers, as it does after HH signaling.
Results: Prior to HH signaling, GLI3 binds to poised, accessible regions with histone deacetylase (HDAC) proteins, similar to post-HH signaling. Despite GLI3 binding to most regions as it does in the post-HH limb, loss of Gli3 is unable to prematurely active target genes or enhancers. Furthermore, we find that GLI3-dependent chromatin compaction does not occur until roughly 10 hours after HH signaling would have normally been induced. Collectively, these results support that GLI repressor proteins are inert prior to HH pathway activation.
 
Overall design ChIP-seq, CUT&RUN, CUT&Tag, ATAC-seq and RNA-seq on pre-HH (E9.25, 21-23S) and post-HH (E10.5, 32-25S) forelimb buds.
 
Contributor(s) Lex RK, Zhou W, Ji H, Vokes SA
Citation(s) 35145123, 37805104
Submission date Jun 24, 2021
Last update date Jan 24, 2025
Contact name Steven A. Vokes
E-mail(s) svokes@austin.utexas.edu
Organization name University of Texas at Austin
Department Molecular Biosciences
Street address 2500 Speedway, STOP A5000
City Austin
State/province Texas
ZIP/Postal code 78757
Country USA
 
Platforms (4)
GPL16417 Illumina MiSeq (Mus musculus)
GPL19057 Illumina NextSeq 500 (Mus musculus)
GPL21103 Illumina HiSeq 4000 (Mus musculus)
Samples (67)
GSM5398884 E9_GLI3_CnR_rep1
GSM5398885 E9_GLI3_CnR_rep2
GSM5398886 E10.5_GLI3_CnR_rep1
Relations
BioProject PRJNA741224
SRA SRP325496

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
GSE178838_RAW.tar 10.4 Gb (http)(custom) TAR (of BIGWIG, BW, TXT)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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