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Series GSE126362 Query DataSets for GSE126362
Status Public on Apr 16, 2019
Title Pax3 cooperates with Ldb1 to direct local chromosome architecture during lineage specification
Organism Mus musculus
Experiment type Genome binding/occupancy profiling by high throughput sequencing
Summary Chromatin looping allows enhancer-bound regulatory factors to influence transcription. Large domains, referred to as Topologically Associated Domains (TADs), participate in genome organization but the mechanisms underlining interactions within TADs, that actually control gene expression, are largely unknown. Here we report that activation of embryonic myogenesis is associated with establishment of long-range chromatin interactions centered on Pax3-bound loci. Using mass spectrometry and genomic studies, we identified the ubiquitously expressed LIM-domain binding protein 1 (Ldb1) as the mediator of looping interactions at a subset of Pax3 binding sites. Ldb1 is recruited to Pax3-bound elements independently of CTCF-Cohesin, and is necessary for efficient deposition of H3K4me1 at these sites and chromatin looping. When Ldb1 is deleted in Pax3-expressing cells in vivo, specification of migratory myogenic progenitors is severely impaired. These results highlight Ldb1 requirement for Pax3 myogenic activity and demonstrate how a transcription factor promotes formation of sub-TAD interactions associated with lineage specification.
Overall design Pax3 doxycycline-inducible murine embryonic stem cells (iPax3) were used to investigate Pax3 function during myogenic lineage specification. ChIP-seq for histone marks was used to characterize the Pax3-bound loci and define enhancers. ChIP-seq for Ldb1, Smc1 and Ctcf was performed to test/validate Pax3-dependent recruitment of these proteins at Pax3-bound sites. HiChIP was used to study chromatin looping at Pax3 bound sites.
Contributor(s) Magli A, Perlingeiro RC, Pota P
Citation(s) 31127120
Submission date Feb 11, 2019
Last update date May 29, 2019
Contact name Alessandro Magli
Organization name University of Minnesota
Department Medicine
Street address 2231 6th St SE
City Minneapolis
State/province MN
ZIP/Postal code 55455
Country USA
Platforms (3)
GPL17021 Illumina HiSeq 2500 (Mus musculus)
GPL21626 NextSeq 550 (Mus musculus)
GPL24247 Illumina NovaSeq 6000 (Mus musculus)
Samples (60)
GSM3597187 ChIPseq_H3K27me3_6day
GSM3597188 ChIPseq_H3K27Ac_6day
GSM3597189 ChIPseq_H3K4me1_6day
BioProject PRJNA521703
SRA SRP185430

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

Supplementary file Size Download File type/resource
GSE126362_1day_plusdox.allValidPairs.hic 434.7 Mb (ftp)(http) HIC
GSE126362_6day_plusdox.allValidPairs.hic 317.3 Mb (ftp)(http) HIC
GSE126362_6day_shLdb1.allValidPairs.hic 476.5 Mb (ftp)(http) HIC
GSE126362_6day_shSCR.allValidPairs.hic 545.3 Mb (ftp)(http) HIC
GSE126362_Ctcf_d4_nodox_noBl.bed.gz 436.1 Kb (ftp)(http) BED
GSE126362_Ctcf_d4_plusdox_noBl.bed.gz 449.0 Kb (ftp)(http) BED
GSE126362_H3K4me1_no_A2_filt_peaks.bed.gz 899.6 Kb (ftp)(http) BED
GSE126362_H3K4me1_no_B2_filt_peaks.bed.gz 957.7 Kb (ftp)(http) BED
GSE126362_H3K4me1_plus_A7_filt_peaks.bed.gz 930.0 Kb (ftp)(http) BED
GSE126362_H3K4me1_plus_B7_filt_peaks.bed.gz 898.5 Kb (ftp)(http) BED
GSE126362_Ldb1_d4_nodox_noBl.bed.gz 56.1 Kb (ftp)(http) BED
GSE126362_Ldb1_d4_plusdox_noBl.bed.gz 40.3 Kb (ftp)(http) BED
GSE126362_RAW.tar 3.9 Gb (http)(custom) TAR (of BED, HIC)
GSE126362_Smc1_d4_nodox_noBl.bed.gz 159.4 Kb (ftp)(http) BED
GSE126362_Smc1_d4_plusdox_noBl.bed.gz 112.6 Kb (ftp)(http) BED
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Raw data are available in SRA
Processed data provided as supplementary file
Processed data are available on Series record

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