UBF Is An Epigenetic Factor Required For Ribosomal RNA Gene Activity And Preinitiation Complex Assembly But Not For Nucleolar Body Formation

Upstream Binding Factor (UBF) is a unique multi-HMGB-box protein first identified as a co-factor in RNA polymerase I (RPI/PolI) transcription. However, its poor DNA sequence selectivity and its ability to generate nucleosome-like nucleoprotein complexes suggest a more generalized role in chromatin structure. We previously showed that extensive depletion of UBF reduced the number of actively transcribed ribosomal RNA (rRNA) genes, but had little effect on rRNA synthesis rates or cell proliferation, leaving open the question of its requirement for RPI transcription. Using conditional gene deletion in mouse, we now show that UBF is indeed essential for transcription of the rRNA genes. Unexpectedly, arrest of rRNA synthesis does not affect RPIII transcription of 5S or tRNA genes, nor RPII expression of the hundreds of mRNAs implicated in ribosome biogenesis, but does upreguglate snRNAs and snoRNAs. Thus, rRNA gene activity does not coordinate global gene expression required for ribosome biogenesis. Conditional UBF flox/flox MEFs and immortalized MEFs and isogenic controls all carrying homozygous ER-Cre alleles were treated with 4-HT and mRNA analyzedat 0h and at 24h intervals posttreatment over 4 days.