Identification of target genes for the transcription factor Elk-1 and its role in cell fate determination

2000 ◽  
Vol 28 (5) ◽  
pp. A243-A243
Author(s):  
E. R. Vickers ◽  
A. D. Sharrocks
Keyword(s):  
Transcription Factor ◽  
Cell Fate ◽  
Target Genes ◽  
Cell Fate Determination ◽  
Fate Determination

scholarly journals Jagged–Delta asymmetry in Notch signaling can give rise to a Sender/Receiver hybrid phenotype

2015 ◽  
Vol 112 (5) ◽  
pp. E402-E409 ◽  
Author(s):  
Marcelo Boareto ◽  
Mohit Kumar Jolly ◽  
Mingyang Lu ◽  
José N. Onuchic ◽  
Cecilia Clementi ◽  
...  
Keyword(s):  
Notch Signaling ◽  
Cell Fate ◽  
Target Genes ◽  
Tumor Stroma ◽  
Notch Receptor ◽  
Toggle Switch ◽  
Cell Fate Determination ◽  
Asymmetric Effect ◽  
Fate Determination

Notch signaling pathway mediates cell-fate determination during embryonic development, wound healing, and tumorigenesis. This pathway is activated when the ligand Delta or the ligand Jagged of one cell interacts with the Notch receptor of its neighboring cell, releasing the Notch Intracellular Domain (NICD) that activates many downstream target genes. NICD affects ligand production asymmetrically––it represses Delta, but activates Jagged. Although the dynamical role of Notch–Jagged signaling remains elusive, it is widely recognized that Notch–Delta signaling behaves as an intercellular toggle switch, giving rise to two distinct fates that neighboring cells adopt––Sender (high ligand, low receptor) and Receiver (low ligand, high receptor). Here, we devise a specific theoretical framework that incorporates both Delta and Jagged in Notch signaling circuit to explore the functional role of Jagged in cell-fate determination. We find that the asymmetric effect of NICD renders the circuit to behave as a three-way switch, giving rise to an additional state––a hybrid Sender/Receiver (medium ligand, medium receptor). This phenotype allows neighboring cells to both send and receive signals, thereby attaining similar fates. We also show that due to the asymmetric effect of the glycosyltransferase Fringe, different outcomes are generated depending on which ligand is dominant: Delta-mediated signaling drives neighboring cells to have an opposite fate; Jagged-mediated signaling drives the cell to maintain a similar fate to that of its neighbor. We elucidate the role of Jagged in cell-fate determination and discuss its possible implications in understanding tumor–stroma cross-talk, which frequently entails Notch–Jagged communication.

PIASγ controls stability and facilitates SUMO-2 conjugation to CoREST family of transcriptional co-repressors

2018 ◽  
Vol 475 (8) ◽  
pp. 1441-1454
Author(s):  
Julián Esteban Sáez ◽  
Cristian Arredondo ◽  
Carlos Rivera ◽  
María Estela Andrés
Keyword(s):  
Cell Fate ◽  
Target Genes ◽  
Protein Complexes ◽  
Control Cell ◽  
E3 Ligase ◽  
Cell Fate Determination ◽  
Fate Determination ◽  
Sumo Protease ◽  
Protein Levels ◽  
The Stability

CoREST family of transcriptional co-repressors regulates gene expression and cell fate determination during development. CoREST co-repressors recruit with different affinity the histone demethylase LSD1 (KDM1A) and the deacetylases HDAC1/2 to repress with variable strength the expression of target genes. CoREST protein levels are differentially regulated during cell fate determination and in mature tissues. However, regulatory mechanisms of CoREST co-repressors at the protein level have not been studied. Here, we report that CoREST (CoREST1, RCOR1) and its homologs CoREST2 (RCOR2) and CoREST3 (RCOR3) interact with PIASγ (protein inhibitor of activated STAT), a SUMO (small ubiquitin-like modifier)-E3-ligase. PIASγ increases the stability of CoREST proteins and facilitates their SUMOylation by SUMO-2. Interestingly, the SUMO-conjugating enzyme, Ubc9 also facilitates the SUMOylation of CoREST proteins. However, it does not change their protein levels. Specificity was shown using the null enzymatic form of PIASγ (PIASγ-C342A) and the SUMO protease SENP-1, which reversed SUMOylation and the increment of CoREST protein levels induced by PIASγ. The major SUMO acceptor lysines are different and are localized in nonconserved sequences among CoREST proteins. SUMOylation-deficient CoREST1 and CoREST3 mutants maintain a similar interaction profile with LSD1 and HDAC1/2, and consequently maintain similar repressor capacity compared with wild-type counterparts. In conclusion, CoREST co-repressors form protein complexes with PIASγ, which acts both as SUMO E3-ligase and as a protein stabilizer for CoREST proteins. This novel regulation of CoREST by PIASγ interaction and SUMOylation may serve to control cell fate determination during development.

scholarly journals Identification of Three Early Phases of Cell-Fate Determination during Osteogenic and Adipogenic Differentiation by Transcription Factor Dynamics

2017 ◽  
Vol 8 (4) ◽  
pp. 947-960 ◽  
Author(s):  
Jeroen van de Peppel ◽  
Tanja Strini ◽  
Julia Tilburg ◽  
Hans Westerhoff ◽  
Andre J. van Wijnen ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Cell Fate ◽  
Adipogenic Differentiation ◽  
Cell Fate Determination ◽  
Fate Determination ◽  
Early Phases

scholarly journals Evidence for additive and synergistic action of mammalian enhancers during cell fate determination

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Jinmi Choi ◽  
Kseniia Lysakovskaia ◽  
Gregoire Stik ◽  
Carina Demel ◽  
Johannes Söding ◽  
...  
Keyword(s):  
Cell Fate ◽  
Target Genes ◽  
Human Leukemia ◽  
Cell Fate Determination ◽  
Cell Type ◽  
Enhancer Activity ◽  
Fate Determination ◽  
Enhancer Rna ◽  
Cell Type Specific ◽  
Factor C

Enhancer activity drives cell differentiation and cell fate determination, but it remains unclear how enhancers cooperate during these processes. Here we investigate enhancer cooperation during transdifferentiation of human leukemia B-cells to macrophages. Putative enhancers are established by binding of the pioneer factor C/EBPα followed by chromatin opening and enhancer RNA (eRNA) synthesis from H3K4-monomethylated regions. Using eRNA synthesis as a proxy for enhancer activity, we find that most putative enhancers cooperate in an additive way to regulate transcription of assigned target genes. However, transcription from 136 target genes depends exponentially on the summed activity of its putative paired enhancers, indicating that these enhancers cooperate synergistically. The target genes are cell type-specific, suggesting that enhancer synergy can contribute to cell fate determination. Enhancer synergy appears to depend on cell type-specific transcription factors, and such interacting enhancers are not predicted from occupancy or accessibility data that are used to detect superenhancers.

scholarly journals GLABRA2, a Common Regulator for Epidermal Cell Fate Determination and Anthocyanin Biosynthesis in Arabidopsis

2019 ◽  
Vol 20 (20) ◽  
pp. 4997 ◽  
Author(s):  
Siyu Chen ◽  
Shucai Wang
Keyword(s):  
Transcription Factor ◽  
Cell Fate ◽  
Epidermal Cell ◽  
Root Hair ◽  
Anthocyanin Biosynthesis ◽  
Research Progress ◽  
Cell Fate Determination ◽  
Fate Determination ◽  
Root Hair Formation ◽  
Hair Formation

Epidermal cell fate determination—including trichome initiation, root hair formation, and flavonoid and mucilage biosynthesis in Arabidopsis (Arabidopsis thaliana)—are controlled by a similar transcriptional regulatory network. In the network, it has been proposed that the MYB-bHLH-WD40 (MBW) activator complexes formed by an R2R3 MYB transcription factor, a bHLH transcription factor and the WD40-repeat protein TRANSPARENT TESTA GLABRA1 (TTG1) regulate the expression of downstream genes required for cell fate determination, flavonoid or mucilage biosynthesis, respectively. In epidermal cell fate determination and mucilage biosynthesis, the MBW activator complexes activate the expression of GLABRA2 (GL2). GL2 is a homeodomain transcription factor that promotes trichome initiation in shoots, mucilage biosynthesis in seeds, and inhibits root hair formation in roots. The MBW activator complexes also activate several R3 MYB genes. The R3 MYB proteins, in turn, competing with the R2R3 MYBs for binding bHLH transcription factors, therefore inhibiting the formation of the MBW activator complexes, lead to the inhibition of trichome initiation in shoots, and promotion of root hair formation in roots. In flavonoid biosynthesis, the MBW activator complexes activate the expression of the late biosynthesis genes in the flavonoid pathway, resulting in the production of anthocyanins or proanthocyanidins. Research progress in recent years suggests that the transcriptional regulatory network that controls epidermal cell fate determination and anthocyanin biosynthesis in Arabidopsis is far more complicated than previously thought. In particular, more regulators of GL2 have been identified, and GL2 has been shown to be involved in the regulation of anthocyanin biosynthesis. This review focuses on the research progress on the regulation of GL2 expression, and the roles of GL2 in the regulation of epidermal cell fate determination and anthocyanin biosynthesis in Arabidopsis.

scholarly journals Cell Fate Determination Factor DACH1 Inhibits c-Jun–induced Contact-independent Growth

2007 ◽  
Vol 18 (3) ◽  
pp. 755-767 ◽  
Author(s):  
Kongming Wu ◽  
Manran Liu ◽  
Anping Li ◽  
Howard Donninger ◽  
Mahadev Rao ◽  
...  
Keyword(s):  
Dna Synthesis ◽  
Cell Fate ◽  
Transcriptional Repression ◽  
Target Genes ◽  
Cellular Proliferation ◽  
Cell Fate Determination ◽  
Fate Determination ◽  
Multiple Context ◽  
Mediated Contact ◽  
Inhibition Of Dna Synthesis

The cell fate determination factor DACH1 plays a key role in cellular differentiation in metazoans. DACH1 is engaged in multiple context-dependent complexes that activate or repress transcription. DACH1 can be recruited to DNA via the Six1/Eya bipartite transcription (DNA binding/coactivator) complex. c-Jun is a critical component of the activator protein (AP)-1 transcription factor complex and can promote contact-independent growth. Herein, DACH1 inhibited c-Jun–induced DNA synthesis and cellular proliferation. Excision of c-Jun with Cre recombinase, in c-junf1/f1 3T3 cells, abrogated DACH1-mediated inhibition of DNA synthesis. c-Jun expression rescued DACH1-mediated inhibition of cellular proliferation. DACH1 inhibited induction of c-Jun by physiological stimuli and repressed c-jun target genes (cyclin A, β-PAK, and stathmin). DACH1 bound c-Jun and inhibited AP-1 transcriptional activity. c-jun and c-fos were transcriptionally repressed by DACH1, requiring the conserved N-terminal (dac and ski/sno [DS]) domain. c-fos transcriptional repression by DACH1 requires the SRF site of the c-fos promoter. DACH1 inhibited c-Jun transactivation through the δ domain of c-Jun. DACH1 coprecipitated the histone deacetylase proteins (HDAC1, HDAC2, and NCoR), providing a mechanism by which DACH1 represses c-Jun activity through the conserved δ domain. An oncogenic v-Jun deleted of the δ domain was resistant to DACH1 repression. Collectively, these studies demonstrate a novel mechanism by which DACH1 blocks c-Jun-mediated contact-independent growth through repressing the c-Jun δ domain.

scholarly journals Signal Transducer and Activator of Transcription 4 Is Required for the Transcription Factor T-bet to Promote T Helper 1 Cell-Fate Determination

Immunity ◽  
2008 ◽  
Vol 29 (5) ◽  
pp. 679-690 ◽  
Author(s):  
Vivian T. Thieu ◽  
Qing Yu ◽  
Hua-Chen Chang ◽  
Norman Yeh ◽  
Evelyn T. Nguyen ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Cell Fate ◽  
Cell Fate Determination ◽  
Signal Transducer ◽  
T Helper ◽  
T Helper 1 ◽  
Fate Determination

Molecular Mechanisms Underlying the Regulation of Alternate Macrophage and Neutrophil Gene Programs by the Egr Transcription Factors

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4773-4773
Author(s):  
Jason X Cheng ◽  
Peter Laslo ◽  
Chauncey Spooner ◽  
Eric Bertolino ◽  
Harinder Singh
Keyword(s):  
Transcription Factors ◽  
Cell Fate ◽  
Molecular Mechanisms ◽  
Target Genes ◽  
Gene Activity ◽  
Gene Promoters ◽  
Cell Fate Determination ◽  
Fate Determination ◽  
Gene Regulatory ◽  
Progenitor Cell Line

Abstract Cell fate determination in the hematopoietic system involves the onset and resolution of mixed lineage patterns of gene expression. Molecular mechanisms underlying the concerted activation and repression of alternate lineage genes remain to be elucidated. We have proposed a gene regulatory network for macrophage development in which the transcription factors PU.1 and the Egr’s function in a feed forward loop to activate macrophage genes. In the network, the Egr’s counteract the neutrophil regulator Gfi-1 and also repress alternate lineage genes. Using mutant alleles of Egr-1 and Egr-2 we validate the model and demonstrate that the Egr’s are required for initiating but not maintaining the repression of neutrophil genes during macrophage differentiation. Employing a PU.1−/− progenitor cell line we show that PU.1 transiently binds to and activates both macrophage and neutrophil gene promoters thereby leading to the onset of mixed lineage gene activity. While inducing macrophage cell fate determination, PU.1 remains persistently bound to macrophage gene promoters aided by the Egr’s. Surprisingly, the Egr’s displace PU.1 from neutrophil gene promoters by interacting with a co-repressor Nab-2 thereby repressing the alternate lineage program. We propose that the Egr’s have evolved to molecularly discriminate distinct sets of target genes and delineate divergent patterns of gene activity.

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