ArticleInternational journal of molecular sciences2021
ESR1 ChIP-Seq Identifies Distinct Ligand-Free ESR1 Genomic Binding Sites in Human Hepatocytes and Liver Tissue.
Article in International journal of molecular sciences, 2021. 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, 19 citations in OpenAlex.
- Multi-omic analysis of the liver-breast axis reveals key hepatic mediators of breast cancer progression.Science China. Life sciences · 2026Review
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- FOXM1 cooperates with ERα to regulate functional β-cell mass.American journal of physiology. Endocrinology and metabolism · 2025Article
- Unexpected nuclear hormone receptor and chromatin dynamics regulate estrous cycle dependent gene expression.Nucleic acids research · 2024Article
- Bioinformatics and machine learning driven key genes screening for hepatocellular carcinoma.Biochemistry and biophysics reports · 2024Article
- Baohuoside I inhibits FXR signaling pathway to interfere with bile acid homeostasis via targeting ER α degradation.Cell biology and toxicology · 2023Article
- The Role of Estrogen Receptors in Health and Disease.International journal of molecular sciences · 2023Article
- Role of Estrogen Receptor α in Aging and Chronic Disease.Advances in geriatric medicine and research · 2023Article
- Regulatory variants in a novel distal enhancer regulate the expression of CYP3A4 and CYP3A5.Clinical and translational science · 2022Article
- Hepatic adropin is regulated by estrogen and contributes to adverse metabolic phenotypes in ovariectomized mice.Molecular metabolism · 2022Article
- Transcriptional Regulation of Carboxylesterase 1 in Human Liver: Role of the Nuclear Receptor Subfamily 1 Group H Member 3 and Its Splice Isoforms.Drug metabolism and disposition: the biological fate of chemicals · 2022Article
- Genome-wide microRNA profiles identify miR-107 as a top miRNA associating with expression of the CYP3As and other drug metabolizing cytochrome P450 enzymes in the liver.Frontiers in pharmacology · 2022Article
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
The estrogen receptor alpha (ESR1) is an important gene transcriptional regulator, known to mediate the effects of estrogen. Canonically, ESR1 is activated by its ligand estrogen. However, the role of unliganded ESR1 in transcriptional regulation has been gaining attention. We have recently shown that ligand-free ESR1 is a key regulator of several cytochrome P450 (CYP) genes in the liver, however ligand-free ESR1 has not been characterized genome-wide in the human liver. To address this, ESR1 ChIP-Seq was conducted in human liver samples and in hepatocytes with or without 17beta-estradiol (E2) treatment. We identified both ligand-dependent and ligand-independent binding sites throughout the genome. These two ESR1 binding categories showed different genomic localization, pathway enrichment, and cofactor colocalization, indicating different ESR1 regulatory function depending on ligand availability. By analyzing existing ESR1 data from additional human cell lines, we uncovered a potential ligand-independent ESR1 activity, namely its co-enrichment with the zinc finger protein 143 (ZNF143). Furthermore, we identified ESR1 binding sites near many gene loci related to drug therapy, including the CYPs. Overall, this study shows distinct ligand-free and ligand-bound ESR1 chromatin binding profiles in the liver and suggests the potential broad influence of ESR1 in drug metabolism and drug therapy.
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