ArticleProceedings of the National Academy of Sciences of the United States of America2013
ARID4A and ARID4B regulate male fertility, a functional link to the AR and RB pathways.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed, 71 citations in OpenAlex.
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- Arid4a Suppresses Breast Tumor Metastasis by Enhancing MTSS1 Expression via mRNA Stability.Cancer medicine · 2025Article
- In silico exploring of the epigenetic factors in teratozoospermia: A focus onMolecular biology research communications · 2025Article
- Experimental Evaluation of a Direct Fitness Effect of the De Novo Evolved Mouse Gene Pldi.Genome biology and evolution · 2024Article
- Heterozygous Knockout ofGenes · 2023Article
- Epigenetics, cryptorchidism, and infertility.Basic and clinical andrology · 2023Article
- Molecular Characterization of Patients with Cryptorchidism: Preliminary Search for an Expression Profile Related to That of Testicular Germ-Cell Tumors.Diagnostics (Basel, Switzerland) · 2023Article
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- Unveiling the molecular structure and role of RBBP4/7: implications for epigenetic regulation and cancer research.Frontiers in molecular biosciences · 2023Review
- Gene profiling reveals the role of inflammation, abnormal uterine muscle contraction and vascularity in recurrent implantation failure.Frontiers in genetics · 2023Article
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- A novel heterozygous missense variant of the ARID4A gene identified in Han Chinese families with schizophrenia-diagnosed siblings that interferes with DNA-binding activity.Molecular psychiatry · 2022Article
- Missense Variants Reveal Functional Insights Into the Human ARID Family of Gene Regulators.Journal of molecular biology · 2022Article
- Sertoli Cell-Germ Cell Interactions Within the Niche: Paracrine and Juxtacrine Molecular Communications.Frontiers in endocrinology · 2022Review
- What Does Androgen Receptor Signaling Pathway in Sertoli Cells During Normal Spermatogenesis Tell Us?Frontiers in endocrinology · 2022Review
- ARID4B is critical for mouse embryonic stem cell differentiation towards mesoderm and endoderm, linking epigenetics to pluripotency exit.The Journal of biological chemistry · 2020Article
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
ARID4A and ARID4B are homologous members of the ARID (AT-rich interaction domain) gene family. ARID4A and ARID4B physically interact with each other. ARID4A is a retinoblastoma (RB)-binding protein. Biological function of these interactions is still unknown. Here, we report that mice with complete deficiency of Arid4a, combined with haploinsufficiency of Arid4b (Arid4a(-/-)Arid4b(+/-)), showed progressive loss of male fertility, accompanied by hypogonadism and seminal vesicle agenesis/hypodysplasia. Arid4a and Arid4b are expressed mainly in Sertoli cells of testes, which implies that their roles in Sertoli cell function are to support spermatogenesis and create the impermeable blood-testis barrier. In fact, evaluation of germ cell development in the Arid4a(-/-)Arid4b(+/-) mice showed spermatogenic arrest at the stages of meiotic spermatocytes and postmeiotic haploid spermatids. Analysis of the integrity of the blood-testis barrier showed increased permeability of seminiferous tubules in the Arid4a(-/-)Arid4b(+/-) testes. Interestingly, phenotypic Sertoli cell dysfunction in the Arid4a(-/-)Arid4b(+/-) mice, including spermatogenic failures and the impaired blood-testis barrier, recapitulated the defects found in the Sertoli cell-specific androgen receptor (AR) knockout mice and the Sertoli cell-specific RB knockout mice. Investigation of the molecular mechanism identified several AR- and RB-responsive genes as downstream targets of ARID4A and ARID4B. Our results thus indicate that ARID4A and ARID4B function as transcriptional coactivators for AR and RB and play an integral part in the AR and RB regulatory pathways involved in the regulation of Sertoli cell function and male fertility.
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