Next generation sequencing facilitates lineage identity of RA-induced and RA/CHIR-induced ESCs
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA509431 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR8311540_1.fastq.gz | Fastqsanger.gz | |||
| SRR8311540_2.fastq.gz | Fastqsanger.gz | |||
| SRR8311550_1.fastq.gz | Fastqsanger.gz | |||
| SRR8311550_2.fastq.gz | Fastqsanger.gz | |||
| SRR8311560_1.fastq.gz | Fastqsanger.gz |
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Project 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.
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