scholarly journals Phospho-signal flow from a pole-localized microdomain spatially patterns transcription factor activity

2017 ◽  
Author(s):  
Keren Lasker ◽  
Alex von Diezmann ◽  
Daniel G. Ahrens ◽  
Thomas H. Mann ◽  
W. E. Moerner ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Cell Fate ◽  
Single Molecule ◽  
Transcriptional Activation ◽  
Intracellular Signaling ◽  
Caulobacter Crescentus ◽  
Transcriptional Profiling ◽  
Reaction Diffusion ◽  
Single Molecule Tracking ◽  
Daughter Cells

SUMMARYSelective recruitment and concentration of signaling proteins within membrane-less compartments is a ubiquitous mechanism for subcellular organization. However, little is known about how such dynamic recruitment patterns intracellular signaling and cellular development. Here, we combined transcriptional profiling, reaction-diffusion modeling, and single-molecule tracking to study signal exchange in and out of a microdomain at the cell pole of the asymmetrically dividing bacteriumCaulobacter crescentus.Our study revealed that the microdomain is selectively permeable, and that each protein in the signaling pathway that activates the cell fate transcription factor CtrA is sequestered and uniformly concentrated within the microdomain or its proximal membrane. Restricted rates of entry into and escape from the microdomain enhance phospho-signaling, leading to a sublinear gradient of CtrA~P along the long axis of the cell. The spatial patterning of CtrA~P creates a gradient of transcriptional activation that serves to prime asymmetric development of the two daughter cells.

scholarly journals The WT1-like transcription factor Klumpfuss maintains lineage commitment of enterocyte progenitors in the Drosophila intestine

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Jerome Korzelius ◽  
Sina Azami ◽  
Tal Ronnen-Oron ◽  
Philipp Koch ◽  
Maik Baldauf ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Cell Differentiation ◽  
Cell Fate ◽  
Progenitor Cell ◽  
Lineage Commitment ◽  
Proneural Gene ◽  
Cell Lineages ◽  
Daughter Cells ◽  
Mechanistic Insight ◽  
Insight Into

Abstract In adult epithelial stem cell lineages, the precise differentiation of daughter cells is critical to maintain tissue homeostasis. Notch signaling controls the choice between absorptive and entero-endocrine cell differentiation in both the mammalian small intestine and the Drosophila midgut, yet how Notch promotes lineage restriction remains unclear. Here, we describe a role for the transcription factor Klumpfuss (Klu) in restricting the fate of enteroblasts (EBs) in the Drosophila intestine. Klu is induced in Notch-positive EBs and its activity restricts cell fate towards the enterocyte (EC) lineage. Transcriptomics and DamID profiling show that Klu suppresses enteroendocrine (EE) fate by repressing the action of the proneural gene Scute, which is essential for EE differentiation. Loss of Klu results in differentiation of EBs into EE cells. Our findings provide mechanistic insight into how lineage commitment in progenitor cell differentiation can be ensured downstream of initial specification cues.

scholarly journals The WT1-like transcription factor Klumpfuss maintains lineage commitment in the intestine

2019 ◽  
Author(s):  
Jerome Korzelius ◽  
Tal Ronnen-Oron ◽  
Maik Baldauf ◽  
Elke Meier ◽  
Pedro Sousa-Victor ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Cell Fate ◽  
Feedback Loop ◽  
Common Mechanism ◽  
Cell Fates ◽  
Daughter Cells ◽  
Transient Activation ◽  
Transient Activity ◽  
Temporal Restriction ◽  
High Degree

AbstractStem cell (SC) lineages in barrier epithelia exhibit a high degree of plasticity. Mechanisms that govern the precise specification of SC daughter cells during regenerative episodes are therefore critical to maintain homeostasis. One such common mechanism is the transient activation of the Notch (N) signaling pathway. N controls the choice between absorptive and entero-endocrine cell fates in both the mammalian small intestine and theDrosophilamidgut, yet how precisely N signaling promotes lineage restriction in progenitor cells remains unclear. Here, we describe a role for the WT1-like transcription factor Klumpfuss (Klu) in restricting the fate ofDrosophilaenteroblasts (EBs) downstream of N activation. Klu is transiently induced in Notch-positive EBs and its transient activity restricts cell fate towards the enterocyte (EC) lineage. Transcriptomics and DamID profiling show that Klu suppresses enteroendocrine (EE) cell fates by repressing E(Spl)m8-HLH and Phyllopod, both negative regulators of the proneural gene Scute, which is essential for EE differentiation. At the same time, Klu suppresses cell cycle genes, committing EBs to differentiation. Klu-mediated repression of its own transcription further sets up a negative feedback loop that ensures temporal restriction of Klu-mediated gene regulation, and is essential for subsequent differentiation of ECs. Our findings define a transient cell state in which EC lineage restriction is cemented, and establish a hierarchy of transcriptional programs critical in executing a differentiation program downstream of initial induction events governed by N signaling.

scholarly journals Time-resolved transcriptomics in neural stem cells identifies a v-ATPase/Notch regulatory loop

2018 ◽  
Vol 217 (9) ◽  
pp. 3285-3300 ◽  
Author(s):  
Sebastian Wissel ◽  
Heike Harzer ◽  
François Bonnay ◽  
Thomas R. Burkard ◽  
Ralph A. Neumüller ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Neural Stem Cells ◽  
Cell Fate ◽  
Cell Biology ◽  
Transcriptional Profiling ◽  
Nervous System Development ◽  
Time Resolved ◽  
Daughter Cells ◽  
Regulatory Loop

Drosophila melanogaster neural stem cells (neuroblasts [NBs]) divide asymmetrically by differentially segregating protein determinants into their daughter cells. Although the machinery for asymmetric protein segregation is well understood, the events that reprogram one of the two daughter cells toward terminal differentiation are less clear. In this study, we use time-resolved transcriptional profiling to identify the earliest transcriptional differences between the daughter cells on their way toward distinct fates. By screening for coregulated protein complexes, we identify vacuolar-type H+–ATPase (v-ATPase) among the first and most significantly down-regulated complexes in differentiating daughter cells. We show that v-ATPase is essential for NB growth and persistent activity of the Notch signaling pathway. Our data suggest that v-ATPase and Notch form a regulatory loop that acts in multiple stem cell lineages both during nervous system development and in the adult gut. We provide a unique resource for investigating neural stem cell biology and demonstrate that cell fate changes can be induced by transcriptional regulation of basic, cell-essential pathways.

scholarly journals Nanos promotes epigenetic reprograming of the germline by down-regulation of the THAP transcription factor LIN-15B

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Chih-Yung Sean Lee ◽  
Tu Lu ◽  
Geraldine Seydoux
Keyword(s):  
Transcription Factor ◽  
Cell Fate ◽  
Transcriptional Activation ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Primordial Germ Cells ◽  
Germline Development ◽  
C Elegans ◽  
Maternal Transcripts ◽  
Underlying Mechanisms

Nanos RNA-binding proteins are required for germline development in metazoans, but the underlying mechanisms remain poorly understood. We have profiled the transcriptome of primordial germ cells (PGCs) lacking the nanos homologs nos-1 and nos-2 in C. elegans. nos-1nos-2 PGCs fail to silence hundreds of transcripts normally expressed in oocytes. We find that this misregulation is due to both delayed turnover of maternal transcripts and inappropriate transcriptional activation. The latter appears to be an indirect consequence of delayed turnover of the maternally-inherited transcription factor LIN-15B, a synMuvB class transcription factor known to antagonize PRC2 activity. PRC2 is required for chromatin reprogramming in the germline, and the transcriptome of PGCs lacking PRC2 resembles that of nos-1nos-2 PGCs. Loss of maternal LIN-15B restores fertility to nos-1nos-2 mutants. These findings suggest that Nanos promotes germ cell fate by downregulating maternal RNAs and proteins that would otherwise interfere with PRC2-dependent reprogramming of PGC chromatin.

Genome-Wide Transcript Profiling Reveals an Auxin-Responsive Transcription Factor, OsAP2/ERF-40, Promoting Rice Adventitious Root Development

2019 ◽  
Vol 60 (10) ◽  
pp. 2343-2355 ◽  
Author(s):  
Ananya Neogy ◽  
Tushar Garg ◽  
Anil Kumar ◽  
Anuj K Dwivedi ◽  
Harshita Singh ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Signaling Pathways ◽  
Cell Fate ◽  
Transcriptional Activation ◽  
Adventitious Root ◽  
Grass Species ◽  
Ethylene Response Factor ◽  
Hormone Signaling ◽  
Developmental Program ◽  
Genome Wide

Abstract Unlike dicots, the robust root system in grass species largely originates from stem base during postembryonic development. The mechanisms by which plant hormone signaling pathways control the architecture of adventitious root remain largely unknown. Here, we studied the modulations in global genes activity in developing rice adventitious root by genome-wide RNA sequencing in response to external auxin and cytokinin signaling cues. We further analyzed spatiotemporal regulations of key developmental regulators emerged from our global transcriptome analysis. Interestingly, some of the key cell fate determinants such as homeodomain transcription factor (TF), OsHOX12, no apical meristem protein, OsNAC39, APETALA2/ethylene response factor, OsAP2/ERF-40 and WUSCHEL-related homeobox, OsWOX6.1 and OsWOX6.2, specifically expressed in adventitious root primordia. Functional analysis of one of these regulators, an auxin-induced TF containing AP2/ERF domain, OsAP2/ERF-40, demonstrates its sufficiency to confer the adventitious root fate. The ability to trigger the root developmental program is largely attributed to OsAP2/ERF-40-mediated dose-dependent transcriptional activation of genes that can facilitate generating effective auxin response, and OsERF3–OsWOX11–OsRR2 pathway. Our studies reveal gene regulatory network operating in response to hormone signaling pathways and identify a novel TF regulating adventitious root developmental program, a key agronomically important quantitative trait, upstream of OsERF3–OsWOX11–OsRR2 pathway.

scholarly journals Divest Yourself of a Preconceived Idea: Transcription Factor ATF6 Is Not a Soluble Protein!

2010 ◽  
Vol 21 (9) ◽  
pp. 1435-1438 ◽  
Author(s):  
Kazutoshi Mori
Keyword(s):  
Transcription Factor ◽  
Er Stress ◽  
Transcriptional Activation ◽  
Intracellular Signaling ◽  
Leucine Zipper ◽  
Transmembrane Protein ◽  
Basic Leucine Zipper ◽  
Induction Program ◽  
Activating Transcription Factor ◽  
The Unfolded Protein Response

The unfolded protein response (UPR), an evolutionarily conserved transcriptional induction program that is coupled with intracellular signaling from the endoplasmic reticulum (ER) to the nucleus, is activated to cope with ER stress and to maintain the homeostasis of the ER. In 1996, we isolated a basic leucine zipper protein, which had been previously named activating transcription factor (ATF)6, as a candidate transcription factor responsible for the mammalian UPR. Subsequent analysis, however, was confounding. The problem was eventually tracked down to an unusual property of ATF6: rather than being a soluble nuclear protein, as expected for an active transcription factor, ATF6 was instead synthesized as a transmembrane protein embedded in the ER, which was activated by ER stress-induced proteolysis. ATF6 was thus unique: an ER stress sensor/transducer that is involved in all steps of the UPR, from the sensing step in the ER to the transcriptional activation step in the nucleus.

scholarly journals Asymmetric enrichment of PIE-1 in the Caenorhabditis elegans zygote mediated by binary counterdiffusion

2009 ◽  
Vol 184 (4) ◽  
pp. 473-479 ◽  
Author(s):  
Brian R. Daniels ◽  
Edward M. Perkins ◽  
Terrence M. Dobrowsky ◽  
Sean X. Sun ◽  
Denis Wirtz
Keyword(s):  
Caenorhabditis Elegans ◽  
Cell Fate ◽  
Heterogeneous Reaction ◽  
Reaction Diffusion ◽  
Developmental Potential ◽  
Daughter Cells ◽  
Reaction Diffusion Model ◽  
Fate Determinants ◽  
Cell Fate Determinants ◽  
Enrichment Process

To generate cellular diversity in developing organisms while simultaneously maintaining the developmental potential of the germline, germ cells must be able to preferentially endow germline daughter cells with a cytoplasmic portion containing specialized cell fate determinants not inherited by somatic cells. In Caenorhabditis elegans, germline inheritance of the protein PIE-1 is accomplished by first asymmetrically localizing the protein to the germplasm before cleavage and subsequently degrading residual levels of the protein in the somatic cytoplasm after cleavage. Despite its critical involvement in cell fate determination, the enrichment of germline determinants remains poorly understood. Here, combining live-cell fluorescence methods and kinetic modeling, we demonstrate that the enrichment process does not involve protein immobilization, intracellular compartmentalization, or localized protein degradation. Instead, our results support a heterogeneous reaction/diffusion model for PIE-1 enrichment in which the diffusion coefficient of PIE-1 is reversibly reduced in the posterior, resulting in a stable protein gradient across the zygote at steady state.

Subnuclear compartmentalization of sequence-specific transcription factors and regulation of eukaryotic gene expression

2005 ◽  
Vol 83 (4) ◽  
pp. 535-547 ◽  
Author(s):  
Gareth N Corry ◽  
D Alan Underhill
Keyword(s):  
Gene Expression ◽  
Transcription Factor ◽  
Transcription Factors ◽  
Transcriptional Activation ◽  
Current Knowledge ◽  
Nuclear Architecture ◽  
Subnuclear Localization ◽  
Modular Structures

To date, the majority of the research regarding eukaryotic transcription factors has focused on characterizing their function primarily through in vitro methods. These studies have revealed that transcription factors are essentially modular structures, containing separate regions that participate in such activities as DNA binding, protein–protein interaction, and transcriptional activation or repression. To fully comprehend the behavior of a given transcription factor, however, these domains must be analyzed in the context of the entire protein, and in certain cases the context of a multiprotein complex. Furthermore, it must be appreciated that transcription factors function in the nucleus, where they must contend with a variety of factors, including the nuclear architecture, chromatin domains, chromosome territories, and cell-cycle-associated processes. Recent examinations of transcription factors in the nucleus have clarified the behavior of these proteins in vivo and have increased our understanding of how gene expression is regulated in eukaryotes. Here, we review the current knowledge regarding sequence-specific transcription factor compartmentalization within the nucleus and discuss its impact on the regulation of such processes as activation or repression of gene expression and interaction with coregulatory factors.Key words: transcription, subnuclear localization, chromatin, gene expression, nuclear architecture.

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