scholarly journals Inner nuclear protein Matrin-3 coordinates cell differentiation by stabilizing chromatin architecture

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Hye Ji Cha ◽  
Özgün Uyan ◽  
Yan Kai ◽  
Tianxin Liu ◽  
Qian Zhu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Differentiation ◽  
Cell Fate ◽  
Nuclear Protein ◽  
Embryonic Stem ◽  
Chromatin Organization ◽  
Scaffolding Protein ◽  
Control Of Gene Expression ◽  
Precise Control ◽  
Matrin 3

AbstractPrecise control of gene expression during differentiation relies on the interplay of chromatin and nuclear structure. Despite an established contribution of nuclear membrane proteins to developmental gene regulation, little is known regarding the role of inner nuclear proteins. Here we demonstrate that loss of the nuclear scaffolding protein Matrin-3 (Matr3) in erythroid cells leads to morphological and gene expression changes characteristic of accelerated maturation, as well as broad alterations in chromatin organization similar to those accompanying differentiation. Matr3 protein interacts with CTCF and the cohesin complex, and its loss perturbs their occupancy at a subset of sites. Destabilization of CTCF and cohesin binding correlates with altered transcription and accelerated differentiation. This association is conserved in embryonic stem cells. Our findings indicate Matr3 negatively affects cell fate transitions and demonstrate that a critical inner nuclear protein impacts occupancy of architectural factors, culminating in broad effects on chromatin organization and cell differentiation.

scholarly journals Distinct roles for CDK-Mediator in controlling Polycomb-dependent chromosomal interactions and priming genes for induction

2021 ◽  
Author(s):  
Emilia Dimitrova ◽  
Angelika Feldmann ◽  
Robin H van der Weide ◽  
Koen D Flach ◽  
Anna Lastuvkova ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gene Activation ◽  
Embryonic Stem ◽  
Regulatory Elements ◽  
Gene Promoters ◽  
Control Of Gene Expression ◽  
Precise Control ◽  
3D Genome ◽  
Gene Regulatory Elements ◽  
Gene Regulatory

Precise control of gene expression underpins normal development. This relies on mechanisms that enable communication between gene promoters and other regulatory elements. In embryonic stem cells (ESCs), the CDK-Mediator (CDK-MED) complex has been reported to physically link gene regulatory elements to enable gene expression and also prime genes for induction during differentiation. Here we discover that CDK-MED contributes little to 3D genome organisation in ESCs, but has a specific and essential role in controlling interactions between inactive gene regulatory elements bound by Polycomb repressive complexes (PRCs). These interactions are established by the canonical PRC1 (cPRC1) complex but rely on CDK-MED, which facilitates binding of cPRC1 to its target sites. Importantly, through separation of function experiments, we reveal that this collaboration between CDK-MED and cPRC1 in creating long-range interactions does not function to prime genes for induction during differentiation. Instead, we discover that priming relies on an interaction-independent mechanism whereby the CDK module supports core Mediator engagement with gene promoters to enable gene activation.

Concentration-dependent gene expression responses to flusilazole in embryonic stem cell differentiation cultures

2011 ◽  
Vol 251 (2) ◽  
pp. 110-118 ◽  
Author(s):  
Dorien A.M. van Dartel ◽  
Jeroen L.A. Pennings ◽  
Liset J.J. de la Fonteyne ◽  
Karen J.J. Brauers ◽  
Sandra Claessen ◽  
...  
Keyword(s):  
Gene Expression ◽  
Stem Cell ◽  
Cell Differentiation ◽  
Embryonic Stem Cell ◽  
Embryonic Stem ◽  
Stem Cell Differentiation ◽  
Embryonic Stem Cell Differentiation

scholarly journals Generative modeling of single-cell population time series for inferring cell differentiation landscapes

2020 ◽  
Author(s):  
Grace H.T. Yeo ◽  
Sachit D. Saksena ◽  
David K. Gifford
Keyword(s):  
Gene Expression ◽  
Time Series ◽  
Cell Differentiation ◽  
Single Cell ◽  
Cell Fate ◽  
Lineage Tracing ◽  
Model Framework ◽  
Modeling Framework ◽  
Generative Modeling ◽  
Model Complex

SummaryExisting computational methods that use single-cell RNA-sequencing for cell fate prediction either summarize observations of cell states and their couplings without modeling the underlying differentiation process, or are limited in their capacity to model complex differentiation landscapes. Thus, contemporary methods cannot predict how cells evolve stochastically and in physical time from an arbitrary starting expression state, nor can they model the cell fate consequences of gene expression perturbations. We introduce PRESCIENT (Potential eneRgy undErlying Single Cell gradIENTs), a generative modeling framework that learns an underlying differentiation landscape from single-cell time-series gene expression data. Our generative model framework provides insight into the process of differentiation and can simulate differentiation trajectories for arbitrary gene expression progenitor states. We validate our method on a recently published experimental lineage tracing dataset that provides observed trajectories. We show that this model is able to predict the fate biases of progenitor cells in neutrophil/macrophage lineages when accounting for cell proliferation, improving upon the best-performing existing method. We also show how a model can predict trajectories for cells not found in the model’s training set, including cells in which genes or sets of genes have been perturbed. PRESCIENT is able to accommodate complex perturbations of multiple genes, at different time points and from different starting cell populations. PRESCIENT models are able to recover the expected effects of known modulators of cell fate in hematopoiesis and pancreatic β cell differentiation.

scholarly journals Genome expression dynamics reveals parasitism regulatory landscape of the root-knot nematode Meloidogyne incognita and a promoter motif associated with effector genes

2021 ◽  
Author(s):  
Martine Da Rocha ◽  
Caroline Bournaud ◽  
Julie Dazeniere ◽  
Peter Thorpe ◽  
Clement Pellegrin ◽  
...  
Keyword(s):  
Gene Expression ◽  
Meloidogyne Incognita ◽  
Life Stage ◽  
Regulation Of Gene Expression ◽  
Root Knot Nematode ◽  
Root Knot Nematodes ◽  
Control Of Gene Expression ◽  
Precise Control ◽  
Effector Genes ◽  
Spatio Temporal

Root-knot nematodes are the major contributor to the crop losses caused by nematodes. Root-knot nematodes secrete effectors into the plant, derived from two sets of pharyngeal gland cells, to manipulate host physiology and immunity. Successful completion of the life cycle, involving successive molts from egg to adult, covers morphologically and functionally distinct stages and will require precise control of gene expression, including effectors. The details of how root-knot nematodes regulate transcription remain sparse. Here, we report a life stage-specific transcriptome of Meloidogyne incognita. Combined with an available annotated genome, we explore the spatio-temporal regulation of gene expression. We reveal gene expression clusters and predicted functions that accompany the major developmental transitions. Focusing on effectors, we identify a putative cis-regulatory motif associated with expression in the dorsal glands: providing an insight into effector regulation. We combine the presence of this motif with several other criteria to predict a novel set of putative dorsal gland effectors. Finally, we show this motif, and thereby its utility, is broadly conserved across the Meloidogyne genus and termed it Mel-DOG. Taken together, we provide the first genome-wide analysis of spatio-temporal gene expression in a root-knot nematode, and identify a new set of candidate effector genes that will guide future functional analyses.

Engineering Gene Control Circuits with Allosteric Ribozymes in Human Cells as a Medicine of the Future

2013 ◽  
pp. 860-883
Author(s):  
Robert Penchovsky
Keyword(s):  
Gene Expression ◽  
Cell Fate ◽  
Regulatory Networks ◽  
Control Of Gene Expression ◽  
Practical Applications ◽  
Gene Therapies ◽  
Sequencing Technologies ◽  
The Future ◽  
Control Circuits ◽  
Exogenous Control

Systems and synthetic biology promise to develop new approaches for analysis and design of complex gene expression regulatory networks in living cells with many practical applications to the pharmaceutical and biotech industries. In this chapter the development of novel universal strategies for exogenous control of gene expression is discussed. They are based on designer allosteric ribozymes that can function in the cell. The synthetic riboswitches are obtained by a patented computational procedure that provides fast and accurate modular designs with various Boolean logic functions. The riboswitches can be designed to sense in the cell either the presence or the absence of disease indicative RNA(s) or small molecules, and to switch on or off the gene expression of any exogenous protein. In addition, the riboswitches can be engineered to induce RNA interference or microRNA pathways that can conditionally down regulate the expression of key proteins in the cell. That can prevent a disease’s development. Therefore, the presented synthetic riboswitches can be used as truly universal cellular biosensors. Nowadays, disease indicative RNA(s) can be precisely identified by employing next-generation sequencing technologies with high accuracy . The methods can be employed not only for exogenous control of gene expression but also for re-programming the cell fate, anticancer, and antiviral gene therapies. Such approaches may be employed as potent molecular medicines of the future.

scholarly journals Evaluation of Developmental Toxicant Identification Using Gene Expression Profiling in Embryonic Stem Cell Differentiation Cultures

2010 ◽  
Vol 119 (1) ◽  
pp. 126-134 ◽  
Author(s):  
Dorien A. M. van Dartel ◽  
Jeroen L. A. Pennings ◽  
Liset J. J. de la Fonteyne ◽  
Karen J. J. Brauers ◽  
Sandra Claessen ◽  
...  
Keyword(s):  
Gene Expression ◽  
Stem Cell ◽  
Cell Differentiation ◽  
Embryonic Stem Cell ◽  
Gene Expression Profiling ◽  
Expression Profiling ◽  
Embryonic Stem ◽  
Stem Cell Differentiation ◽  
Embryonic Stem Cell Differentiation

scholarly journals MicroRNAs: From Female Fertility, Germ Cells, and Stem Cells to Cancer in Humans

2016 ◽  
Vol 2016 ◽  
pp. 1-17 ◽  
Author(s):  
Irma Virant-Klun ◽  
Anders Ståhlberg ◽  
Mikael Kubista ◽  
Thomas Skutella
Keyword(s):  
Gene Expression ◽  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Germ Cells ◽  
Noncoding Rna ◽  
Ovarian Function ◽  
Embryonic Stem ◽  
Cell Communication ◽  
Female Fertility ◽  
Control Of Gene Expression

MicroRNAs are a family of naturally occurring small noncoding RNA molecules that play an important regulatory role in gene expression. They are suggested to regulate a large proportion of protein encoding genes by mediating the translational suppression and posttranscriptional control of gene expression. Recent findings show that microRNAs are emerging as important regulators of cellular differentiation and dedifferentiation, and are deeply involved in developmental processes including human preimplantation development. They keep a balance between pluripotency and differentiation in the embryo and embryonic stem cells. Moreover, it became evident that dysregulation of microRNA expression may play a fundamental role in progression and dissemination of different cancers including ovarian cancer. The interest is still increased by the discovery of exosomes, that is, cell-derived vesicles, which can carry different proteins but also microRNAs between different cells and are involved in cell-to-cell communication. MicroRNAs, together with exosomes, have a great potential to be used for prognosis, therapy, and biomarkers of different diseases including infertility. The aim of this review paper is to summarize the existent knowledge on microRNAs related to female fertility and cancer: from primordial germ cells and ovarian function, germinal stem cells, oocytes, and embryos to embryonic stem cells.

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