Accession |
PRJCA011597 |
Title |
A distal enhancer maintaining Hoxa1 expression orchestrates retinoic acid-induced early ESCs differentiation |
Relevance |
Medical |
Data types |
Raw sequence reads
|
Organisms |
Mus musculus
|
Description |
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. |
Sample scope |
Multiisolate |
Release date |
2022-09-02 |
Publication |
PubMed ID |
Article title |
Journal name |
DOI |
Year |
|
A distal enhancer maintaining Hoxa1 expression orchestrates retinoic acid-induced early ESCs differentiation
|
Nucleic Acids Research
|
10.1093/nar/gkz482
|
2019
|
|
Grants |
Agency |
program |
Grant ID |
Grant title |
Ministry of Science and Technology of the People's Republic of China (MOST)
|
National Key Technologies R&D Program
|
2017YFA0102600
|
|
|
Accessions in other database |
Accession |
Database name |
SRP174196
|
NCBI
|
|
Submitter |
Wenbin
Wang (sciencedb@gibh.ac.cn)
|
Organization |
Nankai University |
Submission date |
2022-09-01 |