ArticleNucleic acids research2019
A distal enhancer maintaining Hoxa1 expression orchestrates retinoic acid-induced early ESCs differentiation.
Article in Nucleic acids research, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 23 citations in OpenAlex.
- Review
- Dysregulation of HOXA genes in acute myeloid leukemia and targeted therapy.NPJ precision oncology · 2025Review
- The role of HOXA1 in cancer and targeted therapy.Medical oncology (Northwood, London, England) · 2025Review
- Klf5-adjacent super-enhancer functions as a 3D genome structure-dependent transcriptional driver to safeguard ESC identity.Nature communications · 2025Article
- H3K4me1 facilitates promoter-enhancer interactions and gene activation during embryonic stem cell differentiation.Molecular cell · 2024Article
- Abnormal Fetal Lung of Hoxa1Animals : an open access journal from MDPI · 2023Article
- Enhancer architecture-dependent multilayered transcriptional regulation orchestrates RA signaling-induced early lineage differentiation of ESCs.Nucleic acids research · 2021Article
- Regulation Network of Colorectal-Cancer-Specific Enhancers in the Progression of Colorectal Cancer.International journal of molecular sciences · 2021Article
- Pontin Functions as A Transcriptional Co-activator for Retinoic Acid-induced HOX Gene Expression.Journal of molecular biology · 2021Article
- Bio-inspired chiral self-assemblies promoted neuronal differentiation of retinal progenitor cells through activation of metabolic pathway.Bioactive materials · 2021Article
- AGenome research · 2020Article
- Review
- CTCF-binding element regulates ESC differentiation via orchestrating long-range chromatin interaction between enhancers and HoxA.The Journal of biological chemistryArticle
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Retinoic acid (RA) induces rapid differentiation of embryonic stem cells (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 genes expression and then orchestrates RA-induced early differentiation of ESCs. This discovery reveals mechanisms of a novel enhancer regulating RA-induced Hoxa genes expression and early ESCs differentiation.
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