scholarly journals Expression of an activated rasD gene changes cell fate decisions during Dictyostelium development.

1997 ◽  
Vol 8 (2) ◽  
pp. 303-312 ◽  
Author(s):  
S A Louis ◽  
G B Spiegelman ◽  
G Weeks
Keyword(s):  
Gene Expression ◽  
Cell Fate ◽  
Cell Mass ◽  
Cell Formation ◽  
Specific Gene ◽  
Wild Type ◽  
Multicellular Development ◽  
Cell Fate Decisions ◽  
Prespore Cell

It has been previously demonstrated that the expression of an activated rasD gene in wild-type Dictyostelium cells results in formation of aggregates with multitips, instead of the normal single tips, and a block in further development. In an attempt to better understand the role of activated RasD development, we examined cell-type-specific gene expression in a strain stably expressing high levels of RasD[G12T]. We found that the expression of prestalk cell-specific genes ecmA and tagB was markedly enhanced, whereas the expression of the prespore cell-specific gene cotC was reduced to very low levels. When the fate of cells in the multitipped aggregate was monitored with an ecmA/lacZ fusion, it appeared that most of the cells eventually adopted prestalk gene expression characteristics. When mixtures of the [G12T]rasD cells and Ax3 cells were induced to differentiate, chimeric pseudoplasmodia were not formed. Thus, although the [G12T]rasD transformant had a marked propensity to form prestalk cells, it could not supply the prestalk cell population when mixed with wild-type cells. Both stalk and spore cell formation occurred in low cell density monolayers of the [G12T]rasD strain, suggesting that at least part of the inhibition of stalk and spore formation during multicellular development involved inhibitory cell interactions within the cell mass. Models for the possible role of rasD in development are discussed.

Identification and analysis of a gene that is essential for morphogenesis and prespore cell differentiation in Dictyostelium

Development ◽  
1998 ◽  
Vol 125 (14) ◽  
pp. 2565-2576 ◽  
Author(s):  
H. Yasukawa ◽  
S. Mohanty ◽  
R.A. Firtel
Keyword(s):  
Gene Expression ◽  
Cell Differentiation ◽  
Cell Fate ◽  
Stalk Cell ◽  
Specific Gene ◽  
Wild Type ◽  
Cell Type ◽  
Primary Defect ◽  
Experimental Conditions ◽  
Prespore Cell

We have identified a gene (PslA) that is expressed throughout Dictyostelium development and encodes a novel protein that is required for proper aggregation and subsequent cell-type differentiation and morphogenesis. pslA null (pslA-) cells produce large aggregation streams under conditions in which wild-type cells form discrete aggregates. Tips form along the stream, elongate to produce a finger, and eventually form a terminal structure that lacks a true sorus (spore head). More than half of the cells remain as a mass at the base of the developing fingers. The primary defect in the pslA- strain is the inability to induce prespore cell differentiation. Analyses of gene expression show a complete lack of prespore-specific gene expression and no mature spores are produced. In chimeras with wild-type cells, pslA- cells form the prestalk domain and normal, properly proportioned fruiting bodies can be produced. This indicates that pslA- cells are able to interact with wild-type cells and regulate patterning, even though pslA- cells are unable to express prespore cell-type-specific genes, do not participate in prespore cell differentiation and do not produce pslA- spores in the chimeras. While pslA- cells produce mature, vacuolated stalk cells during multicellular development, pslA- cells are unable to do so in vitro in response to exogenous DIF (a morphogen required for prestalk and stalk cell differentiation). These results indicate that pslA- cells exhibit a defect in the prestalk/stalk cell pathways under these experimental conditions. Our results suggest that PslA's primary function is to regulate prespore cell determination very early in the prespore pathway via a cell-autonomous mechanism, possibly at the time of the initial prestalk/prespore cell-fate decision. Indirect immunofluorescence of myc-tagged PslA localizes the protein to the nucleus, suggesting that PslA may function to control the prespore pathway at the level of transcription.

scholarly journals Functional Promiscuity of Gene Regulation by Serpentine Receptors in Dictyostelium discoideum

1998 ◽  
Vol 18 (10) ◽  
pp. 5744-5749 ◽  
Author(s):  
Irene Verkerke-Van Wijk ◽  
Ji-Yun Kim ◽  
Raymond Brandt ◽  
Peter N. Devreotes ◽  
Pauline Schaap
Keyword(s):  
Gene Expression ◽  
Cell Fate ◽  
Dictyostelium Discoideum ◽  
Developmental Regulation ◽  
Mutant Cell ◽  
Gene Induction ◽  
Specific Gene ◽  
Wild Type ◽  
Animal Development ◽  
Camp Stimulation

ABSTRACT Serpentine receptors such as smoothened and frizzled play important roles in cell fate determination during animal development. InDictyostelium discoideum, four serpentine cyclic AMP (cAMP) receptors (cARs) regulate expression of multiple classes of developmental genes. To understand their function, it is essential to know whether each cAR is coupled to a specific gene regulatory pathway or whether specificity results from the different developmental regulation of individual cARs. To distinguish between these possibilities, we measured gene induction in car1 car3 double mutant cell lines that express equal levels of either cAR1, cAR2, or cAR3 under a constitutive promoter. We found that all cARs efficiently mediate both aggregative gene induction by cAMP pulses and induction of postaggregative and prespore genes by persistent cAMP stimulation. Two exceptions to this functional promiscuity were observed. (i) Only cAR1 can mediate adenosine inhibition of cAMP-induced prespore gene expression, a phenomenon that was found earlier in wild-type cells. cAR1’s mediation of adenosine inhibition suggests that cAR1 normally mediates prespore gene induction. (ii) Only cAR2 allows entry into the prestalk pathway. Prestalk gene expression is induced by differentiation-inducing factor (DIF) but only after cells have been prestimulated with cAMP. We found that DIF-induced prestalk gene expression is 10 times higher in constitutive cAR2 expressors than in constitutive cAR1 or cAR3 expressors (which still have endogenous cAR2), suggesting that cAR2 mediates induction of DIF competence. Since in wild-type slugs cAR2 is expressed only in anterior cells, this could explain the so far puzzling observations that prestalk cells differentiate at the anterior region but that DIF levels are actually higher at the posterior region. After the initial induction of DIF competence, cAMP becomes a repressor of prestalk gene expression. This function can again be mediated by cAR1, cAR2, and cAR3.

scholarly journals C/EBPα determines hematopoietic cell fate in multipotential progenitor cells by inhibiting erythroid differentiation and inducing myeloid differentiation

Blood ◽  
2006 ◽  
Vol 107 (11) ◽  
pp. 4308-4316 ◽  
Author(s):  
Hyung Chan Suh ◽  
John Gooya ◽  
Katie Renn ◽  
Alan D. Friedman ◽  
Peter F. Johnson ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Fate ◽  
Hematopoietic Cell ◽  
Myeloid Differentiation ◽  
Specific Gene ◽  
Erythroid Progenitors ◽  
Hematopoietic Stem ◽  
Cell Fate Decisions ◽  
Conditional Expression ◽  
Murine Erythroleukemia

AbstractC/EBPα is an essential transcription factor required for myeloid differentiation. While C/EBPα can act as a cell fate switch to promote granulocyte differentiation in bipotential granulocyte-macrophage progenitors (GMPs), its role in regulating cell fate decisions in more primitive progenitors is not known. We found increased numbers of erythroid progenitors and erythroid cells in C/EBPα–/– fetal liver (FL). Also, enforced expression of C/EBPα in hematopoietic stem cells resulted in a loss of erythroid progenitors and an increase in myeloid cells by inhibition of erythroid development and inducing myeloid differentiation. Conditional expression of C/EBPα in murine erythroleukemia (MEL) cells induced myeloid-specific genes, while inhibiting erythroid-specific gene expression including erythropoietin receptor (EpoR), which suggests a novel mechanism to determine hematopoietic cell fate. Thus, C/EBPα functions in hematopoietic cell fate decisions by the dual actions of inhibiting erythroid and inducing myeloid gene expression in multipotential progenitors.

scholarly journals TET-Mediated Epigenetic Regulation in Immune Cell Development and Disease

2021 ◽  
Vol 8 ◽  
Author(s):  
Nikolas James Tsiouplis ◽  
David Wesley Bailey ◽  
Lilly Felicia Chiou ◽  
Fiona Jane Wissink ◽  
Ageliki Tsagaratou
Keyword(s):  
Gene Expression ◽  
Cell Fate ◽  
Immune Cell ◽  
Cell Development ◽  
Dna Demethylation ◽  
Oxidation Products ◽  
Specific Gene ◽  
Loss Of Function ◽  
Cell Fate Decisions ◽  
Tet Proteins

TET proteins oxidize 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC) and further oxidation products in DNA. The oxidized methylcytosines (oxi-mCs) facilitate DNA demethylation and are also novel epigenetic marks. TET loss-of-function is strongly associated with cancer; TET2 loss-of-function mutations are frequently observed in hematological malignancies that are resistant to conventional therapies. Importantly, TET proteins govern cell fate decisions during development of various cell types by activating a cell-specific gene expression program. In this review, we seek to provide a conceptual framework of the mechanisms that fine tune TET activity. Then, we specifically focus on the multifaceted roles of TET proteins in regulating gene expression in immune cell development, function, and disease.

Altered epidermal growth factor-like sequences provide evidence for a role of Notch as a receptor in cell fate decisions

Development ◽  
1993 ◽  
Vol 117 (3) ◽  
pp. 1113-1123 ◽  
Author(s):  
P. Heitzler ◽  
P. Simpson
Keyword(s):  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Cell Fate ◽  
Cell Interactions ◽  
Signalling Pathway ◽  
Neural Precursor ◽  
Wild Type ◽  
Cell Fate Decisions ◽  
Epidermal Growth

In Drosophila each neural precursor is chosen from a group of cells through cell interactions mediated by Notch and Delta which may function as receptor and ligand (signal), respectively, in a lateral signalling pathway. The cells of a group are equipotential and express both Notch and Delta. Hyperactive mutant Notch molecules, (Abruptex), probably have an enhanced affinity for the ligand. When adjacent to wild-type cells, cells bearing the Abruptex proteins are unable to produce the signal. It is suggested that in addition to the binding of Notch molecules on one cell to the Delta molecules of opposing cells, the Notch and Delta proteins on the surface of the same cell may interact. Binding between a cell's own Notch and Delta molecules would alter the availability of these proteins to interact with their counterparts on adjacent cells.

scholarly journals PRMT6 activates cyclin D1 expression in conjunction with the transcription factor LEF1

Oncogenesis ◽  
2021 ◽  
Vol 10 (5) ◽  
Author(s):  
Lucas Schneider ◽  
Stefanie Herkt ◽  
Lei Wang ◽  
Christine Feld ◽  
Josephine Wesely ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Cycle ◽  
Transcription Factors ◽  
Cyclin D1 ◽  
Cell Fate ◽  
Target Genes ◽  
Specific Gene ◽  
Cell Fate Decisions ◽  
Rational Development ◽  
Differentiation And Proliferation

AbstractThe establishment of cell type specific gene expression by transcription factors and their epigenetic cofactors is central for cell fate decisions. Protein arginine methyltransferase 6 (PRMT6) is an epigenetic regulator of gene expression mainly through methylating arginines at histone H3. This way it influences cellular differentiation and proliferation. PRMT6 lacks DNA-binding capability but is recruited by transcription factors to regulate gene expression. However, currently only a limited number of transcription factors have been identified, which facilitate recruitment of PRMT6 to key cell cycle related target genes. Here, we show that LEF1 contributes to the recruitment of PRMT6 to the central cell cycle regulator CCND1 (Cyclin D1). We identified LEF1 as an interaction partner of PRMT6. Knockdown of LEF1 or PRMT6 reduces CCND1 expression. This is in line with our observation that knockdown of PRMT6 increases the number of cells in G1 phase of the cell cycle and decreases proliferation. These results improve the understanding of PRMT6 activity in cell cycle regulation. We expect that these insights will foster the rational development and usage of specific PRMT6 inhibitors for cancer therapy.

scholarly journals Super-Enhancers and CTCF in Early Embryonic Cell Fate Decisions

2021 ◽  
Vol 9 ◽  
Author(s):  
Puja Agrawal ◽  
Sridhar Rao
Keyword(s):  
Gene Expression ◽  
Cell Fate ◽  
Critical Role ◽  
Regulatory Elements ◽  
Specific Gene ◽  
Cell Type ◽  
Mammalian Development ◽  
Cell Fate Decisions ◽  
Cell Type Specific ◽  
Early Mammalian Development

Cell fate decisions are the backbone of many developmental and disease processes. In early mammalian development, precise gene expression changes underly the rapid division of a single cell that leads to the embryo and are critically dependent on autonomous cell changes in gene expression. To understand how these lineage specifications events are mediated, scientists have had to look past protein coding genes to the cis regulatory elements (CREs), including enhancers and insulators, that modulate gene expression. One class of enhancers, termed super-enhancers, is highly active and cell-type specific, implying their critical role in modulating cell-type specific gene expression. Deletion or mutations within these CREs adversely affect gene expression and development and can cause disease. In this mini-review we discuss recent studies describing the potential roles of two CREs, enhancers and binding sites for CTCF, in early mammalian development.

Characterization of a Megakaryocyte-Specific Enhancer of the Key Hemopoietic Transcription Factor GATA1.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 834-834
Author(s):  
Boris Guyot ◽  
Kasumi Murai ◽  
Yuko Fujiwara ◽  
Veronica Valverde-Garduno ◽  
Michele Hammett ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transcription Factor ◽  
Dna Binding ◽  
Transgenic Mice ◽  
Cell Fate ◽  
Red Cells ◽  
Specific Gene ◽  
Cell Fate Decisions

Abstract Specification and differentiation of the megakaryocyte and erythroid lineages from a common bipotential progenitor provides a well-studied model to dissect binary cell fate decisions. To understand how the distinct megakaryocyte- and erythroid-specific gene programs arise, we have examined the transcriptional regulation of the transcription factor GATA1, that is required for normal maturation of these two lineages. Megakaryocyte- and erythroid-specific mouse (m)GATA1 expression requires the mGata1 enhancer mHS-3.5. Within mHS-3.5, we previously showed that the 3′ 179 base pairs (bp) of mHS-3.5 are required for megakaryocyte but not red cell expression. Here, we show that mHS-3.5 binds key hemopoietic transcription factors in vivo (GATA1, SCL/TAL-1) and is required to maintain histone acetylation in the mGata1 locus in primary megakaryocytes. When deletional constructs containing mHS-3.5 were used to direct GATA1-LacZ reporter gene expression in transgenic mice, a 25 bp element within the 3′ 179bp in mHS-3.5, was critical for megakaryocyte expression. In vitro three uncharacterized DNA-binding activities A, B and C bind to the core of the 25 bp element, and these binding sites are conserved through evolution. Of these, only activity B is present in primary megakaryocytes but not red cells. Furthermore, mutation analysis in transgenic mice reveals that activity B is required for megakaryocyte-specific enhancer function. Bioinformatic analysis shows that sequence corresponding to the binding site for activity B is a previously unrecognised motif present in the cis-elements of other megakaryocyte-specific genes. In summary, we have identified a motif and a DNA-binding activity that are likely to be important in directing a megakaryocyte gene expression program distinct from that in red cells.

scholarly journals The Interplay Between Chromatin Architecture and Lineage-Specific Transcription Factors and the Regulation of Rag Gene Expression

2021 ◽  
Vol 12 ◽  
Author(s):  
Kazuko Miyazaki ◽  
Masaki Miyazaki
Keyword(s):  
Gene Expression ◽  
Transcription Factors ◽  
Cell Fate ◽  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Specific Gene ◽  
Cell Type ◽  
Cell Fate Decisions ◽  
Chromatin Architecture ◽  
Cell Type Specific

Cell type-specific gene expression is driven through the interplay between lineage-specific transcription factors (TFs) and the chromatin architecture, such as topologically associating domains (TADs), and enhancer-promoter interactions. To elucidate the molecular mechanisms of the cell fate decisions and cell type-specific functions, it is important to understand the interplay between chromatin architectures and TFs. Among enhancers, super-enhancers (SEs) play key roles in establishing cell identity. Adaptive immunity depends on the RAG-mediated assembly of antigen recognition receptors. Hence, regulation of the Rag1 and Rag2 (Rag1/2) genes is a hallmark of adaptive lymphoid lineage commitment. Here, we review the current knowledge of 3D genome organization, SE formation, and Rag1/2 gene regulation during B cell and T cell differentiation.

Tracing the origin of the placental trophoblast cells in mouse embryo development†

2019 ◽  
Vol 102 (3) ◽  
pp. 598-606
Author(s):  
Shanshan Guo ◽  
Xiuhong Cui ◽  
Xiangxiang Jiang ◽  
Shuguang Duo ◽  
Shiwen Li ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Fate ◽  
Inner Cell Mass ◽  
Expression Patterns ◽  
Cell Mass ◽  
Cell Fates ◽  
Cell Stage ◽  
Mouse Fetus ◽  
Cell Fate Decisions ◽  
Distinct Cell

Abstract The placenta, which originates from the trophectoderm (TE), is the first organ to form during mammalian embryogenesis. Recent studies based on bioinformatics analysis have revealed that heterogeneous gene expression initiates cell-fate decisions and directs two distinct cell fates by modulating the balance of pluripotency and differentiation as early as the four-cell stage. However, direct developmental evidence to support this is still lacking. To address at which stage the cell fate of the TE and inner cell mass (ICM) is determined, in this study, we administered a microinjection of Cre mRNA into a single blastomere of the mTmG mouse at different cleavage stages before implantation to examine the distributions of the descendants of the single-labeled cell in the mouse fetus and the placenta at E12.5. We found that the descendants of the labeled cells at the two-cell stage contributed to both the placenta and the fetus. Notably, the derivatives of the labeled cells at the four-cell stage fell into three categories: (1) distributed in both embryonic and extraembryonic lineages, (2) distributed only in mouse placental trophoblast layers, or (3) distributed only in the lineage derived from the ICM. In addition, these results fell in line with single-cell studies focusing on gene expression patterns that characterize particular lineages within the blastocyst. In conclusion, this study shows that the four-cell blastomeres differ in their individual developmental properties insofar as they contribute to either or both the ICM and trophoblast fate.

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