Division of Hematology and Oncology, Department of Medicine.
Department of Cell and Developmental Biology.
Curr Opin Hematol. 2024 Jul 1;31(4):199-206. doi: 10.1097/MOH.0000000000000816. Epub 2024 Apr 11.
PURPOSE OF REVIEW: Ribosomal RNAs (rRNAs) are transcribed within nucleoli from rDNA repeats by RNA Polymerase I (Pol I). There is variation in rRNA transcription rates across the hematopoietic tree, and leukemic blast cells have prominent nucleoli, indicating abundant ribosome biogenesis. The mechanisms underlying these variations are poorly understood. The purpose of this review is to summarize findings of rDNA binding and Pol I regulation by hematopoietic transcription factors. RECENT FINDINGS: Our group recently used custom genome assemblies optimized for human and mouse rDNA mapping to map nearly 2200 ChIP-Seq datasets for nearly 250 factors to rDNA, allowing us to identify conserved occupancy patterns for multiple transcription factors. We confirmed known rDNA occupancy of MYC and RUNX factors, and identified new binding sites for CEBP factors, IRF factors, and SPI1 at canonical motif sequences. We also showed that CEBPA degradation rapidly leads to reduced Pol I occupancy and nascent rRNA in mouse myeloid cells. SUMMARY: We propose that a number of hematopoietic transcription factors bind rDNA and potentially regulate rRNA transcription. Our model has implications for normal and malignant hematopoiesis. This review summarizes the literature, and outlines experimental considerations to bear in mind while dissecting transcription factor roles on rDNA.
综述目的:核糖体 RNA(rRNA)由 RNA 聚合酶 I(Pol I)在核仁内从 rDNA 重复序列转录。造血谱系中 rRNA 转录率存在差异,白血病母细胞有明显的核仁,表明核糖体生物发生丰富。这些变化的机制尚不清楚。本综述的目的是总结造血转录因子对 rDNA 结合和 Pol I 调节的研究结果。
最近的发现:我们的小组最近使用了针对人类和小鼠 rDNA 作图优化的定制基因组组装,对近 250 个因子的近 2200 个 ChIP-Seq 数据集进行了作图,使我们能够识别多个转录因子的保守结合模式。我们证实了 MYC 和 RUNX 因子已知的 rDNA 结合,并且在典型的 motif 序列中鉴定了 CEBP 因子、IRF 因子和 SPI1 的新结合位点。我们还表明,CEBPA 降解会迅速导致小鼠髓系细胞中 Pol I 结合减少和新生 rRNA 减少。
总结:我们提出,许多造血转录因子结合 rDNA,并可能调节 rRNA 转录。我们的模型对正常和恶性造血有影响。本综述总结了文献,并概述了在剖析转录因子在 rDNA 上的作用时需要注意的实验考虑因素。
Curr Opin Hematol. 2024-7-1
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bioRxiv. 2024-10-13
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