Transcription factor regulation of ribosomal RNA in hematopoiesis.

Abstract

Ribosomal RNAs (rRNAs) are transcribed within nucleoli from rDNA repeats by RNA Polymerase I (Pol I). There is variation in rRNA transcription rates across the hematopoietic tree, and leukemic blast cells have prominent nucleoli, indicating abundant ribosome biogenesis. The mechanisms underlying these variations are poorly understood. The purpose of this review is to summarize findings of rDNA binding and Pol I regulation by hematopoietic transcription factors. Our group recently used custom genome assemblies optimized for human and mouse rDNA mapping to map nearly 2200 ChIP-Seq datasets for nearly 250 factors to rDNA, allowing us to identify conserved occupancy patterns for multiple transcription factors. We confirmed known rDNA occupancy of MYC and RUNX factors, and identified new binding sites for CEBP factors, IRF factors, and SPI1 at canonical motif sequences. We also showed that CEBPA degradation rapidly leads to reduced Pol I occupancy and nascent rRNA in mouse myeloid cells. We propose that a number of hematopoietic transcription factors bind rDNA and potentially regulate rRNA transcription. Our model has implications for normal and malignant hematopoiesis. This review summarizes the literature, and outlines experimental considerations to bear in mind while dissecting transcription factor roles on rDNA.