Control of ribosomal RNA synthesis by hematopoietic transcription factors

Mol Cell. 2022 Oct 20;82(20):3826-3839.e9. doi: 10.1016/j.molcel.2022.08.027. Epub 2022 Sep 15.


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: CEBPa; FISH; Polr1; RNA Pol I; RNA polymerase I; dTAG; degron; hematopoiesis; rDNA; rRNA; ribosome biogenesis; transcription factor.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Chromatin
  • DNA, Ribosomal / genetics
  • Humans
  • Mice
  • RNA
  • RNA Polymerase I* / genetics
  • RNA Polymerase I* / metabolism
  • RNA, Ribosomal / genetics
  • Transcription Factors* / genetics
  • Transcription Factors* / metabolism
  • Transcription, Genetic


  • RNA Polymerase I
  • Transcription Factors
  • RNA, Ribosomal
  • DNA, Ribosomal
  • RNA
  • Chromatin