scholarly journals Genomic analysis of COP9 signalosome function in Drosophila melanogaster reveals a role in temporal regulation of gene expression

2007 ◽  
Vol 3 (1) ◽  
pp. 108 ◽  
Author(s):  
Efrat Oron ◽  
Tamir Tuller ◽  
Ling Li ◽  
Nina Rozovsky ◽  
Daniel Yekutieli ◽  
...  
2012 ◽  
Vol 416 (3) ◽  
pp. 389-399 ◽  
Author(s):  
Olga Pavlova ◽  
Daria Lavysh ◽  
Evgeny Klimuk ◽  
Marko Djordjevic ◽  
Dmitry A. Ravcheev ◽  
...  

2010 ◽  
Vol 30 (14) ◽  
pp. 3531-3541 ◽  
Author(s):  
Jonathan A. R. Gordon ◽  
Mohammad Q. Hassan ◽  
Sharanjot Saini ◽  
Martin Montecino ◽  
Andre J. van Wijnen ◽  
...  

ABSTRACT Abdominal-class homeodomain-containing (Hox) factors form multimeric complexes with TALE-class homeodomain proteins (Pbx, Meis) to regulate tissue morphogenesis and skeletal development. Here we have established that Pbx1 negatively regulates Hoxa10-mediated gene transcription in mesenchymal cells and identified components of a Pbx1 complex associated with genes in osteoblasts. Expression of Pbx1 impaired osteogenic commitment of C3H10T1/2 multipotent cells and differentiation of MC3T3-E1 preosteoblasts. Conversely, targeted depletion of Pbx1 by short hairpin RNA (shRNA) increased expression of osteoblast-related genes. Studies using wild-type and mutated osteocalcin and Bsp promoters revealed that Pbx1 acts through a Pbx-binding site that is required to attenuate gene activation by Hoxa10. Chromatin-associated Pbx1 and Hoxa10 were present at osteoblast-related gene promoters preceding gene expression, but only Hoxa10 was associated with these promoters during transcription. Our results show that Pbx1 is associated with histone deacetylases normally linked with chromatin inactivation. Loss of Pbx1 from osteoblast promoters in differentiated osteoblasts was associated with increased histone acetylation and CBP/p300 recruitment, as well as decreased H3K9 methylation. We propose that Pbx1 plays a central role in attenuating the ability of Hoxa10 to activate osteoblast-related genes in order to establish temporal regulation of gene expression during osteogenesis.


Science ◽  
2021 ◽  
Vol 372 (6546) ◽  
pp. 1085-1091
Author(s):  
Débora R. Sobreira ◽  
Amelia C. Joslin ◽  
Qi Zhang ◽  
Iain Williamson ◽  
Grace T. Hansen ◽  
...  

Whereas coding variants often have pleiotropic effects across multiple tissues, noncoding variants are thought to mediate their phenotypic effects by specific tissue and temporal regulation of gene expression. Here, we investigated the genetic and functional architecture of a genomic region within the FTO gene that is strongly associated with obesity risk. We show that multiple variants on a common haplotype modify the regulatory properties of several enhancers targeting IRX3 and IRX5 from megabase distances. We demonstrate that these enhancers affect gene expression in multiple tissues, including adipose and brain, and impart regulatory effects during a restricted temporal window. Our data indicate that the genetic architecture of disease-associated loci may involve extensive pleiotropy, allelic heterogeneity, shared allelic effects across tissues, and temporally restricted effects.


2020 ◽  
Vol 375 (1795) ◽  
pp. 20190341 ◽  
Author(s):  
Judit Salces-Ortiz ◽  
Carlos Vargas-Chavez ◽  
Lain Guio ◽  
Gabriel E. Rech ◽  
Josefa González

Most of the genotype–phenotype analyses to date have largely centred attention on single nucleotide polymorphisms. However, transposable element (TE) insertions have arisen as a plausible addition to the study of the genotypic–phenotypic link because of to their role in genome function and evolution. In this work, we investigate the contribution of TE insertions to the regulation of gene expression in response to insecticides. We exposed four Drosophila melanogaster strains to malathion, a commonly used organophosphate insecticide. By combining information from different approaches, including RNA-seq and ATAC-seq, we found that TEs can contribute to the regulation of gene expression under insecticide exposure by rewiring cis -regulatory networks. This article is part of a discussion meeting issue ‘Crossroads between transposons and gene regulation’.


2015 ◽  
Vol 35 (21) ◽  
pp. 3669-3683 ◽  
Author(s):  
Alessandro Rienzo ◽  
Daniel Poveda-Huertes ◽  
Selcan Aydin ◽  
Nicolas E. Buchler ◽  
Amparo Pascual-Ahuir ◽  
...  

Cells respond to environmental stimuli by fine-tuned regulation of gene expression. Here we investigated the dose-dependent modulation of gene expression at high temporal resolution in response to nutrient and stress signals in yeast. TheGAL1activity in cell populations is modulated in a well-defined range of galactose concentrations, correlating with a dynamic change of histone remodeling and RNA polymerase II (RNAPII) association. This behavior is the result of a heterogeneous induction delay caused by decreasing inducer concentrations across the population. Chromatin remodeling appears to be the basis for the dynamicGAL1expression, because mutants with impaired histone dynamics show severely truncated dose-response profiles. In contrast, theGRE2promoter operates like a rapid off/on switch in response to increasing osmotic stress, with almost constant expression rates and exclusively temporal regulation of histone remodeling and RNAPII occupancy. The Gal3 inducer and the Hog1 mitogen-activated protein (MAP) kinase seem to determine the different dose-response strategies at the two promoters. Accordingly,GAL1becomes highly sensitive and dose independent if previously stimulated because of residual Gal3 levels, whereasGRE2expression diminishes upon repeated stimulation due to acquired stress resistance. Our analysis reveals important differences in the way dynamic signals create dose-sensitive gene expression outputs.


2020 ◽  
Author(s):  
Dingbang Ma ◽  
Dariusz Przybylski ◽  
Katharine C. Abruzzi ◽  
Matthias Schlichting ◽  
Qunlong Li ◽  
...  

AbstractMany different functions are regulated by circadian rhythms, including those orchestrated by discrete clock neurons within animal brains. To comprehensively characterize and assign cell identity to the 75 pairs of Drosophila circadian neurons, we optimized a single cell RNA sequencing method and assayed clock neuron gene expression at different times of day. The data identify at least 17 clock neuron categories with striking spatial regulation of gene expression. Transcription factor regulation is prominent and likely contributes to the robust circadian oscillation of many transcripts, including those that encode cell-surface proteins previously shown to be important for cell recognition and synapse formation during development. We suggest that these molecules orchestrate the temporal regulation of synapse formation and/or strength. The many other clock-regulated genes also constitute an important resource for future mechanistic and functional studies between clock neurons and/or for temporal signaling to circuits elsewhere in the fly brain.


1998 ◽  
Vol 8 (8) ◽  
pp. 475-478 ◽  
Author(s):  
Blanka Rogina ◽  
James W. Vaupel ◽  
Linda Partridge ◽  
Stephen L. Helfand

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