Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

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

ABSTRACT: 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.

ORGANISM(S): Mus musculus

SUBMITTER: Eric Paquet

PROVIDER: E-GEOD-55450 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Conditional inactivation of Upstream Binding Factor reveals its epigenetic functions and the existence of a somatic nucleolar precursor body.

Hamdane Nourdine N Stefanovsky Victor Y VY Tremblay Michel G MG Németh Attila A Paquet Eric E Lessard Frédéric F Sanij Elaine E Hannan Ross R Moss Tom T

PLoS genetics 20140814 8

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 proliferatio ...[more]

PMID: 25121932

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Project description:Disruptions of protein homeostasis in the endoplasmic reticulum (ER) elicit activation of the unfolded protein response (UPR), a translation- and transcription-coupled proteostatic stress response pathway. The primary translational control arm of the UPR is initiated by the PERK-dependent phosphorylation of eIF2Î±, leading to a large-scale reprogramming of translation and subsequent activation of an ATF4-mediated transcriptional program. It has remained challenging, however, to accurately evaluate the contribution of each component of the eIF2Î±/ATF4 pathway to the remodelling of transcription and translation. Here, we have used mouse embryonic fibroblasts containing either a knock-in of the non-phosphorylatable eIF2Î± S51A mutant or knock-out for ATF4 by ribosome profiling and mRNA-seq to define the specific contributions of eIF2Î± phosphoryation and ATF4 in controlling the translational and transcriptional components of the UPR. These studies show that the transcriptional and translational targets of each P-eIF2Î±, ATF4, and the other UPR gene expression programs overlapped extensively, leading to a core set of UPR genes whose robust expression in response to ER stress is driven by multiple mechanisms. The identification of other, more factor-specific targets illustrated the potential for functional specialization of the UPR. As the UPR progressed temporally, cells employed distinct combinations of transcriptional and translational mechanisms, initiated by different factors, to adapt to ongoing stress. These effects were accompanied by a buffering effect where changes in mRNA levels were coupled to opposing changes in ribosome loading, a property which makes cooperation between transcription and translation essential to confer robust protein expression. Translational analysis by ribosome profiling and mRNA-seq of PERK pathways mutants during the UPR. Mouse embryonic fibroblasts (MEFs) lacking components of the PERK pathway (eIF2a phosphorylation and ATF4) were subjected to ER stress and analyzed by ribosome profiling.

Dataset Information

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

Publications

Conditional inactivation of Upstream Binding Factor reveals its epigenetic functions and the existence of a somatic nucleolar precursor body.

Similar Datasets

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