Control of Ribosomal RNA Synthesis by Hematopoietic Transcription Factors

Authors

Charles Antony
Subin S George
Justin Blum
Patrick Somers
Chelsea L Thorsheim
Dexter J Wu-Corts
Yuxi Ai
Long Gao
Kaosheng Lv
Michel G Tremblay
Tom Moss
Kai Tan
Jeremy E Wilusz
Austen R D Ganley
Maxim Pimkin
Vikram R Paralkar

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

Published Open-Access

yes

Keywords

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

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.

Comments

Associated Data