Language

English

Publication Date

10-20-2022

Journal

Molecular Cell

DOI

10.1016/j.molcel.2022.08.027

PMID

36113481

PMCID

PMC9588704

PubMedCentral® Posted Date

10-20-2020

PubMedCentral® Full Text Version

Author MSS

Abstract

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.

Keywords

Humans, Mice, Animals, RNA Polymerase I, Transcription Factors, RNA, Ribosomal, Transcription, Genetic, DNA, Ribosomal, RNA, Chromatin

Published Open-Access

yes

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