ArticleEuropean journal of human genetics : EJHG2016
The sub-nucleolar localization of PHF6 defines its role in rDNA transcription and early processing events.
Article in European journal of human genetics : EJHG, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 28 citations in OpenAlex.
- Nucleoli-localized KANSL2 as an epigenetic regulator of ribosome biogenesis in glioblastoma cells.Communications biology · 2026Article
- Phf6 truncating mutation drives leukemogenesis via disrupted epigenetic regulation in mice.Leukemia · 2026Article
- PHF6 interacts with the LMO2 complex in T-cell acute lymphoblastic leukemia.Haematologica · 2026Article
- Leukemia mutated proteins PHF6 and PHIP form a chromatin complex that represses acute myeloid leukemia stemness.Genes & development · 2025Article
- It Takes a Village of Chromatin Remodelers to Regulate rDNA Expression.International journal of molecular sciences · 2025Review
- PHF6 cooperates with SWI/SNF complexes to facilitate transcriptional progression.Nature communications · 2024Article
- Regulatory roles of nucleolus organizer region-derived long non-coding RNAs.Mammalian genome : official journal of the International Mammalian Genome Society · 2022Review
- PHF6 functions as a tumor suppressor by recruiting methyltransferase SUV39H1 to nucleolar region and offers a novel therapeutic target for PHF6-muntant leukemia.Acta pharmaceutica Sinica. B · 2022Article
- Transgenic mice with an R342X mutation in Phf6 display clinical features of Börjeson-Forssman-Lehmann Syndrome.Human molecular genetics · 2021Article
- Notoginsenoside R1 induces DNA damage via PHF6 protein to inhibit cervical carcinoma cell proliferation.Molecular medicine reports · 2021Article
- Variability of Human rDNA.Cells · 2021Review
- Review
- Loss of PHF6 leads to aberrant development of human neuron-like cells.Scientific reports · 2020Article
- Chromatin regulators and their impact on DNA repair and G2 checkpoint recovery.Cell cycle (Georgetown, Tex.) · 2020Review
- Cockayne syndrome group A and B proteins function in rRNA transcription through nucleolin regulation.Nucleic acids research · 2020Article
- PHF6 promotes non-homologous end joining and G2 checkpoint recovery.EMBO reports · 2020Article
- Review
- Keeping ribosomal DNA intact: a repeating challenge.Chromosome research : an international journal on the molecular, supramolecular and evolutionary aspects of chromosome biology · 2019Review
- The intracellular domain of β-dystroglycan mediates the nucleolar stress response by suppressing UBF transcriptional activity.Cell death & disease · 2019Article
- Deacetylation of NAT10 by Sirt1 promotes the transition from rRNA biogenesis to autophagy upon energy stress.Nucleic acids research · 2018Article
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
Ribosomal RNA synthesis occurs in the nucleolus and is a tightly regulated process that is targeted in some developmental diseases and hyperactivated in multiple cancers. Subcellular localization and immunoprecipitation coupled mass spectrometry demonstrated that a proportion of plant homeodomain (PHD) finger protein 6 (PHF6) protein is localized within the nucleolus and interacts with proteins involved in ribosomal processing. PHF6 sequence variants cause Börjeson-Forssman-Lehmann syndrome (BFLS, MIM#301900) and are also associated with a female-specific phenotype overlapping with Coffin-Siris syndrome (MIM#135900), T-cell acute lymphoblastic leukemia (MIM#613065), and acute myeloid leukemia (MIM#601626); however, very little is known about its cellular function, including its nucleolar role. HEK 293T cells were treated with RNase A, DNase I, actinomycin D, or 5,6-dichloro-β-D-ribofuranosylbenzimadole, followed by immunocytochemistry to determine PHF6 sub-nucleolar localization. We observed RNA-dependent localization of PHF6 to the sub-nucleolar fibrillar center (FC) and dense fibrillar component (DFC), at whose interface rRNA transcription occurs. Subsequent ChIP-qPCR analysis revealed strong enrichment of PHF6 across the entire rDNA-coding sequence but not along the intergenic spacer (IGS) region. When rRNA levels were quantified in a PHF6 gain-of-function model, we observed an overall decrease in rRNA transcription, accompanied by a modest increase in repressive promoter-associated RNA (pRNA) and a significant increase in the expression levels of the non-coding IGS36RNA and IGS39RNA transcripts. Collectively, our results demonstrate a role for PHF6 in carefully mediating the overall levels of ribosome biogenesis within a cell.
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