Conditional Inactivation of Upstream Binding Factor Reveals Its Epigenetic Functions and the Existence of a Somatic Nucleolar Precursor Body

• DOI: 10.1371/journal.pgen.1004505
• Publication Date: 2014-08-14T18:16:08Z
• Authors: Nourdine Hamdane; Victor Y. Stefano...; Michel G. Tremblay; Attila Németh; Eric Paquet; Frédéric Lessard; Elaine Sanij; Ross Hannan; Tom Moss
• Keywords: ribosome biogenesis; Transcription

Upstream Binding Factor (UBF) is a unique multi-HMGB-box protein first identified as co-factor in RNA polymerase I (RPI/PolI) transcription. However, its poor DNA sequence selectivity and ability to generate nucleosome-like nucleoprotein complexes suggest more generalized role chromatin structure. We previously showed that extensive depletion of UBF reduced the number actively transcribed ribosomal (rRNA) genes, but had little effect on rRNA synthesis rates or cell proliferation, leaving open question requirement for RPI Using gene deletion mouse, we now show essential embryo development beyond morula. Conditional cultures reveals also transcription genes it defines active conformation both enhancer sequences. Loss prevents formation SL1/TIF1B pre-initiation complex recruitment RPI-Rrn3/TIF1A complex. It accompanied by H3K9me3, canonical histone H1 HP1α, not de novo methylation. Further, retain penta-acetyl H4 H2A.Z, suggesting even absence can maintain potentially state. In contrast H1, binding H1.4 dependent UBF, strongly plays positive activity. Unexpectedly, arrest does suppress 5S, tRNA snRNA nor expression several hundred mRNA implicated ribosome biogenesis. Thus, activity coordinate global unexpectedly induced cells large sub-nuclear structure resembling nucleolar precursor body (NPB) oocytes early embryos. These somatic NPBs contain processing factors do associate with loci (NORs).