Control of ribosomal RNA synthesis by hematopoietic transcription factors.

Control of ribosomal RNA synthesis by hematopoietic transcription factors.
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DOI:
10.1016/j.molcel.2022.08.027
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发表时间:
2022-10-20
期刊:
影响因子:
16
通讯作者:
Paralkar, Vikram R.
Paralkar, Vikram R.
中科院分区:
生物学1区
文献类型:
--
作者:
Antony, Charles;George, Subin S.;Blum, Justin;Somers, Patrick;Thorsheim, Chelsea L.;Wu-Corts, Dexter J.;Ali, Yuxi;Gao, Long;Lv, Kaosheng;Tremblay, Michel G.;Moss, Tom;Tan, Kai;Wilusz, Jeremy E.;Ganley, Austen R. D.;Pimkin, Maxim;Paralkar, Vikram R.

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Ribosomal RNAs (rRNAs) are the most abundant cellular RNAs, and their synthesis from rDNA repeats by RNA Polymerase I accounts for the bulk of all transcription. Despite substantial variation in rRNA transcription rates across cell types, little is known about cell-type-specific factors that bind rDNA and regulate rRNA transcription to meet tissue-specific needs. Using hematopoiesis as a model system, we mapped about 2200 ChIP-Seq datasets for 250 transcription factors (TFs) and chromatin proteins to human and mouse rDNA, and identified robust binding of multiple TF families to canonical TF motifs on rDNA. Using a 47S-FISH-Flow assay developed for nascent rRNA quantification, we demonstrated that targeted degradation of CEBPA (C/EBP alpha), a critical hematopoietic TF with conserved rDNA binding, caused rapid reduction in rRNA transcription due to reduced Pol I occupancy. Our work identifies numerous potential rRNA regulators, and provides a template for dissection of TF roles in rRNA transcription. Antony et al. mapped existing ChIP-seq datasets to human and mouse rDNA, and identified binding profiles of cell-type specific transcription factors (TFs). The myeloid TF CEBPA bound rDNA at a conserved motif, and its degradation reduced rDNA occupancy of the Pol I-RRN3 complex, and nascent 47S rRNA transcription.
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