ArticleDevelopmental cell2023
RNA polymerase II pausing temporally coordinates cell cycle progression and erythroid differentiation.
Article in Developmental cell, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 32 citations in OpenAlex.
- Regulation of RNA transcript elongation in metazoans and its relevance to disease.Nature reviews. Molecular cell biology · 2026Review
- Mechanisms coordinating exit from the stem cell state in mammals.Genes & development · 2026Review
- TCEA1 Suppresses Acute Promyelocytic Leukemia by Upregulating C/EBPε and IRF8.International journal of molecular sciences · 2026Article
- Cell-type-specific RNA polymerase II activity maps in intact tissues provide a gateway to mammalian gene regulatory mechanisms in vivo.Developmental cell · 2026Article
- Article
- Sequential RNA polymerase II activation drives human hematopoiesis.Cell reports · 2026Article
- Assessing the Impact of Intravascular Hemolysis on Erythropoiesis in Sickle Cell Disease.Methods in molecular biology (Clifton, N.J.) · 2026Article
- Timing is everything: transcription bursting in development.Genes & development · 2025Review
- BRD4 acts as a transcriptional repressor of RhoB to inhibit terminal erythropoiesis.Journal of hematology & oncology · 2025Article
- Promoter-proximal RNA polymerase II termination regulates transcription during human cell type transition.Nature structural & molecular biology · 2025Article
- Histone chaperones coupled to DNA replication and transcription control divergent chromatin elements to maintain cell fate.Genes & development · 2025Article
- Whole-genome relaxed selection and molecular constraints in Triplophysa under adapted Qinghai-Tibetan Plateau.BMC genomics · 2025Article
- Causal modeling of gene effects from regulators to programs to traits: integration of genetic associations and Perturb-seq.bioRxiv : the preprint server for biology · 2025Article
- CRL3Molecular cell · 2024Article
- Activity-assembled nBAF complex mediates rapid immediate early gene transcription by regulating RNA polymerase II productive elongation.Cell reports · 2024Article
- Trans-acting genetic modifiers of clinical severity in heterozygous β-Thalassemia trait.Annals of hematology · 2024Review
- Loss-of-Function Variants inInternational journal of molecular sciences · 2024Review
- Genome-wide quantification of RNA flow across subcellular compartments reveals determinants of the mammalian transcript life cycle.Molecular cell · 2024Article
- Targeted next-generation sequencing and long-read HiFi sequencing provide novel insights into clinically significant KLF1 variants.BMC genomics · 2024Article
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Authors and funding
18 authors at 6 institutions in 3 countries.
Funding
Abstract
Controlled release of promoter-proximal paused RNA polymerase II (RNA Pol II) is crucial for gene regulation. However, studying RNA Pol II pausing is challenging, as pause-release factors are almost all essential. In this study, we identified heterozygous loss-of-function mutations in SUPT5H, which encodes SPT5, in individuals with β-thalassemia. During erythropoiesis in healthy human cells, cell cycle genes were highly paused as cells transition from progenitors to precursors. When the pathogenic mutations were recapitulated by SUPT5H editing, RNA Pol II pause release was globally disrupted, and as cells began transitioning from progenitors to precursors, differentiation was delayed, accompanied by a transient lag in erythroid-specific gene expression and cell cycle kinetics. Despite this delay, cells terminally differentiate, and cell cycle phase distributions normalize. Therefore, hindering pause release perturbs proliferation and differentiation dynamics at a key transition during erythropoiesis, identifying a role for RNA Pol II pausing in temporally coordinating the cell cycle and erythroid differentiation.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.