scholarly journals A Ubiquitin-Conjugating Enzyme Is Essential for Developmental Transitions in Dictyostelium

1997 ◽  
Vol 8 (10) ◽  
pp. 1989-2002 ◽  
Author(s):  
Alexandra Clark ◽  
Anson Nomura ◽  
Sudhasri Mohanty ◽  
Richard A. Firtel
Keyword(s):  
Gene Expression ◽  
Amino Acid ◽  
Amino Acid Sequence ◽  
Specific Gene ◽  
Wild Type ◽  
Cell Type ◽  
Protein Ubiquitination ◽  
High Amino Acid ◽  
Cell Type Specific ◽  
Very High

We have identified a developmentally essential gene,UbcB, by insertional mutagenesis. The encoded protein (UBC1) shows very high amino acid sequence identity to ubiquitin-conjugating enzymes from other organisms, suggesting that UBC1 is involved in protein ubiquitination and possibly degradation during Dictyostelium development. Consistent with the homology of the UBC1 protein to UBCs, the developmental pattern of protein ubiquitination is altered in ubcB-null cells.ubcB-null cells are blocked in the ability to properly execute the developmental transition that occurs between the induction of postaggregative gene expression during mound formation and the induction of cell-type differentiation and subsequent morphogenesis.ubcB-null cells plated on agar form mounds with normal kinetics; however, they remain at this stage for ∼10 h before forming multiple tips and fingers that then arrest. Under other conditions, some of the fingers form migrating slugs, but no culmination is observed. In ubcB-null cells, postaggregative gene transcripts accumulate to very high levels and do not decrease significantly with time as they do in wild-type cells. Expression of cell-type-specific genes is very delayed, with the level of prespore-specific gene expression being significantly reduced compared with that in wild-type cells. lacZ reporter studies using developmentally regulated and cell-type-specific promoters suggest that ubcB-null cells show an unusually elevated level of staining of lacZ reporters expressed in anterior-like cells, a regulatory cell population found scattered throughout the aggregate, and reduced staining of a prespore reporter.ubcB-null cells in a chimeric organism containing predominantly wild-type cells are able to undergo terminal differentiation but show altered spatial localization. In contrast, in chimeras containing only a small fraction of wild-type cells, the mature fruiting body is very small and composed almost exclusively of wild-type cells, with the ubcB-null cells being present as a mass of cells located in extreme posterior of the developing organism. The amino acid sequence analysis of the UbcBopen reading frame (ORF) and the analysis of the developmental phenotypes suggest that tip formation and subsequent development requires specific protein ubiquitination, and possibly degradation.

scholarly journals Abberant chemotaxis and differentiation in Dictyostelium mutant fgdC with a defective regulation of receptor-stimulated phosphoinositidase C

1991 ◽  
Vol 100 (4) ◽  
pp. 825-831 ◽  
Author(s):  
A.A. Bominaar ◽  
F. Kesbeke ◽  
B.E. Snaar-Jagalska ◽  
D.J. Peters ◽  
P. Schaap ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cyclic Amp ◽  
Adenylate Cyclase ◽  
Guanylate Cyclase ◽  
Specific Gene ◽  
Wild Type ◽  
Cell Type ◽  
Surface Receptors ◽  
Cell Type Specific ◽  
Stimulation Of

Dictyostelium cells use extracellular cyclic AMP both as a chemoattractant and as a morphogen inducing cell-type-specific gene expression. Cyclic AMP binds to surface receptors, activates one or more G-proteins, and stimulates adenylate cyclase, guanylate cyclase and phosphoinositidase C. Mutant fgdC showed aberrant chemotaxis, and was devoid of cyclic AMP-induced gene expression and differentiation. Both the receptor- and G-protein-mediated stimulation of adenylate cyclase and guanylate cyclase were unaltered in mutant fgdC as compared to wild-type cells. In wild-type cells phosphoinositidase C was activated about twofold by the cyclic AMP receptor. In mutant fgdC cells, however, the enzyme was inhibited by about 60%. These results suggest that phosphoinositidase C is regulated by a receptor-operated activation/inhibition switch that is defective in mutant fgdC. We conclude that activation of phosphoinositidase C is essential for Dictyostelium development.

scholarly journals Rel Induces Interferon Regulatory Factor 4 (IRF-4) Expression in Lymphocytes

2000 ◽  
Vol 191 (8) ◽  
pp. 1281-1292 ◽  
Author(s):  
Raelene J. Grumont ◽  
Steve Gerondakis
Keyword(s):  
Gene Expression ◽  
Cell Proliferation ◽  
Nuclear Factor Κb ◽  
Wild Type ◽  
Cell Type ◽  
Regulatory Factor ◽  
Specific Manner ◽  
A Cell ◽  
Cell Type Specific ◽  
Interferon Regulatory Factor 4

In lymphocytes, the Rel transcription factor is essential in establishing a pattern of gene expression that promotes cell proliferation, survival, and differentiation. Here we show that mitogen-induced expression of interferon (IFN) regulatory factor 4 (IRF-4), a lymphoid-specific member of the IFN family of transcription factors, is Rel dependent. Consistent with IRF-4 functioning as a repressor of IFN-induced gene expression, the absence of IRF-4 expression in c-rel−/− B cells coincided with a greater sensitivity of these cells to the antiproliferative activity of IFNs. In turn, enforced expression of an IRF-4 transgene restored IFN modulated c-rel−/− B cell proliferation to that of wild-type cells. This cross-regulation between two different signaling pathways represents a novel mechanism that Rel/nuclear factor κB can repress the transcription of IFN-regulated genes in a cell type–specific manner.

scholarly journals Genetic influences on cell type specific gene expression and splicing during neurogenesis elucidate regulatory mechanisms of brain traits

2020 ◽  
Author(s):  
Nil Aygün ◽  
Angela L. Elwell ◽  
Dan Liang ◽  
Michael J. Lafferty ◽  
Kerry E. Cheek ◽  
...  
Keyword(s):  
Gene Expression ◽  
Regulatory Elements ◽  
Regulatory Mechanisms ◽  
Specific Gene ◽  
Cell Type ◽  
Specific Expression ◽  
Risk Variants ◽  
Allele Specific ◽  
Cell Type Specific ◽  
Regulatory Effects

SummaryInterpretation of the function of non-coding risk loci for neuropsychiatric disorders and brain-relevant traits via gene expression and alternative splicing is mainly performed in bulk post-mortem adult tissue. However, genetic risk loci are enriched in regulatory elements of cells present during neocortical differentiation, and regulatory effects of risk variants may be masked by heterogeneity in bulk tissue. Here, we map e/sQTLs and allele specific expression in primary human neural progenitors (n=85) and their sorted neuronal progeny (n=74). Using colocalization and TWAS, we uncover cell-type specific regulatory mechanisms underlying risk for these traits.

scholarly journals Srf destabilizes cellular identity by suppressing cell-type-specific gene expression programs

2018 ◽  
Vol 9 (1) ◽  
Author(s):  
Takashi Ikeda ◽  
Takafusa Hikichi ◽  
Hisashi Miura ◽  
Hirofumi Shibata ◽  
Kanae Mitsunaga ◽  
...  
Keyword(s):  
Gene Expression ◽  
Specific Gene ◽  
Cell Type ◽  
Specific Gene Expression ◽  
Cell Type Specific ◽  
Cellular Identity

New insights into promoter–enhancer communication mechanisms revealed by dynamic single-molecule imaging

2021 ◽  
Author(s):  
Jieru Li ◽  
Alexandros Pertsinidis
Keyword(s):  
Gene Expression ◽  
Single Molecule ◽  
Target Genes ◽  
Regulatory Elements ◽  
Specific Gene ◽  
Single Molecule Imaging ◽  
Cell Type ◽  
Regulatory Information ◽  
Cell Type Specific ◽  
Target Promoters

Establishing cell-type-specific gene expression programs relies on the action of distal enhancers, cis-regulatory elements that can activate target genes over large genomic distances — up to Mega-bases away. How distal enhancers physically relay regulatory information to target promoters has remained a mystery. Here, we review the latest developments and insights into promoter–enhancer communication mechanisms revealed by live-cell, real-time single-molecule imaging approaches.

scholarly journals Using multiple measurements of tissue to estimate subject- and cell-type-specific gene expression

2019 ◽  
Vol 36 (3) ◽  
pp. 782-788 ◽  
Author(s):  
Jiebiao Wang ◽  
Bernie Devlin ◽  
Kathryn Roeder
Keyword(s):  
Gene Expression ◽  
Empirical Bayes ◽  
Brain Regions ◽  
Tissue Level ◽  
Supplementary Information ◽  
Specific Gene ◽  
Expression Data ◽  
Cell Type ◽  
Multiple Measurements ◽  
Cell Type Specific

Abstract Motivation Patterns of gene expression, quantified at the level of tissue or cells, can inform on etiology of disease. There are now rich resources for tissue-level (bulk) gene expression data, which have been collected from thousands of subjects, and resources involving single-cell RNA-sequencing (scRNA-seq) data are expanding rapidly. The latter yields cell type information, although the data can be noisy and typically are derived from a small number of subjects. Results Complementing these approaches, we develop a method to estimate subject- and cell-type-specific (CTS) gene expression from tissue using an empirical Bayes method that borrows information across multiple measurements of the same tissue per subject (e.g. multiple regions of the brain). Analyzing expression data from multiple brain regions from the Genotype-Tissue Expression project (GTEx) reveals CTS expression, which then permits downstream analyses, such as identification of CTS expression Quantitative Trait Loci (eQTL). Availability and implementation We implement this method as an R package MIND, hosted on https://github.com/randel/MIND. Supplementary information Supplementary data are available at Bioinformatics online.

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