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Series GSE124306 Query DataSets for GSE124306
Status Public on Dec 24, 2018
Title A distal enhancer maintaining Hoxa1 expression orchestrates retinoic acid-induced early ESCs differentiation
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary Retinoic acid (RA) induces rapid differentiation of ESCs, partly by activating expression of the transcription factor Hoxa1, which regulates downstream target genes that promote ESCs differentiation. However, mechanisms of RA-induced Hoxa1 expression and ESCs early differentiation remain largely unknown. Here, we identify a distal enhancer interacting with the Hoxa1 locus through a long-range chromatin loop. Enhancer deletion significantly inhibited expression of RA-induced Hoxa1 and endoderm master control genes such as Gata4 and Gata6. Transcriptome analysis revealed that RA-induced early ESCs differentiation was blocked in Hoxa1 enhancer knockout cells, suggesting a requirement for the enhancer. Restoration of Hoxa1 expression partly rescued expression levels of ~40% of genes whose expression changed following enhancer deletion, and ~18% of promoters of those rescued genes were directly bound by Hoxa1. Our data show that a distal enhancer maintains Hoxa1 expression through long-range chromatin loop and that Hoxa1 directly regulates downstream target gene expression and then orchestrates RA-induced early differentiation of ESCs.
Overall design Deep sequencing of three different state cell lines gene expression and interaction of hoxa1 with the genome.
Contributor(s) Su G, Guo D, Lu W
Citation(s) 31147716, 33581110
BioProject PRJNA510884
Submission date Dec 23, 2018
Last update date Mar 23, 2021
Contact name Dianhao Guo
Organization name Nankai University
Street address 94 Weijin Road
City Tianjin
ZIP/Postal code 300071
Country China
Platforms (2)
GPL17021 Illumina HiSeq 2500 (Mus musculus)
GPL21273 HiSeq X Ten (Mus musculus)
Samples (9)
GSM3528714 RNA-Seq of Mus musculus: WT rep-1
GSM3528715 RNA-Seq of Mus musculus: WT rep-2
GSM3528716 RNA-Seq of Mus musculus: EN-KO rep1
SRA SRP174196

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Supplementary file Size Download File type/resource
GSE124306_E14_RA-ed_hoxa1_capture-c_combined_interaction.wig.gz 4.2 Mb (ftp)(http) WIG
GSE124306_E14_RA-induced_hoxa1_enhancer_capture-c_combined_interaction.wig.gz 4.4 Mb (ftp)(http) WIG
GSE124306_E14_RNA_seq_htseq_gene_count_matrix.txt.gz 391.8 Kb (ftp)(http) TXT
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