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Mol Cell ; 82(20): 3826-3839.e9, 2022 10 20.
Artigo em Inglês | MEDLINE | ID: mdl-36113481

RESUMO

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 2,200 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 C/EBP alpha (CEBPA), a critical hematopoietic TF with conserved rDNA binding, caused rapid reduction in rRNA transcription due to reduced RNA Pol I occupancy. Our work identifies numerous potential rRNA regulators and provides a template for dissection of TF roles in rRNA transcription.


Assuntos
RNA Polimerase I , Fatores de Transcrição , Humanos , Camundongos , Animais , RNA Polimerase I/genética , RNA Polimerase I/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , RNA Ribossômico/genética , Transcrição Gênica , DNA Ribossômico/genética , RNA , Cromatina
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