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A distal enhancer maintaining Hoxa1 expression orchestrates retinoic acid-induced early ESCs differentiation

ABSTRACT: 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.

ORGANISM(S): Mus musculus

PROVIDER: GSE124306 | GEO | 2018/12/24

REPOSITORIES: GEO

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2016-02-05 | E-GEOD-76692 | biostudies-arrayexpress

Mus musculus strain:129/Ola

Project description:Hoxa1-regulated Long Noncoding RNAs in Regulating Retinoic Acid-induced ESCs Early Differentiation

| PRJNA512586 | ENA

RA-dependent proximal and distal enhancers’ architecture promotes RA-induced early ESC differentiation

Project description:RA-dependent proximal and distal enhancers’ architecture promotes RA-induced early ESC differentiation

| PRJNA917286 | ENA

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