SoxF factors induce Notch1 expression via direct transcriptional regulation during early arterial development

Chiang, Ivy Kim-Ni; Fritzsche, Martin; Pichol-Thievend, Cathy; Neal, Alice; Holmes, Kelly A.; Lagendijk, Anne Karine; Overman, Jeroen; D'Angelo, Donatella; Omini, Alice; Hermkens, Dorien; Lesieur, Emmanuelle; Liu, Ke; Ratnayaka, Indrika; Corada, Monica; Bou‐Gharios, George; Carroll, Jason S.; Dejana, Elisabetta; Schulte‐Merker, Stefan; Hogan, Benjamin M.; Beltrame, Mônica; Val, Sarah De; François, Mathias

doi:10.1242/dev.146241

Cited by 53 publications

(78 citation statements)

References 70 publications

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“…Antibodies against histone marks, which are highly conserved between species, have been successfully utilized in zebrafish erythrocytes to describe the potential locus control region (LCR) regulating globin expression ( Ganis et al, 2012 ). Moreover, given the functional conservation of these genes, zebrafish is useful to functionally validate enhancers identified in mouse and/or human models ( Tijssen et al, 2011 ; Chiang et al, 2017 ).…”

Section: Identification Of Novel Regulatory Mechanisms Of Normal and mentioning

confidence: 99%

Bloody Zebrafish: Novel Methods in Normal and Malignant Hematopoiesis

Pater

Trompouki

2018

Front. Cell Dev. Biol.

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Hematopoiesis is an optimal system for studying stem cell maintenance and lineage differentiation under physiological and pathological conditions. In vertebrate organisms, billions of differentiated hematopoietic cells need to be continuously produced to replenish the blood cell pool. Disruptions in this process have immediate consequences for oxygen transport, responses against pathogens, maintenance of hemostasis and vascular integrity. Zebrafish is a widely used and well-established model for studying the hematopoietic system. Several new hematopoietic regulators were identified in genetic and chemical screens using the zebrafish model. Moreover, zebrafish enables in vivo imaging of hematopoietic stem cell generation and differentiation during embryogenesis, and adulthood. Finally, zebrafish has been used to model hematopoietic diseases. Recent technological advances in single-cell transcriptome analysis, epigenetic regulation, proteomics, metabolomics, and processing of large data sets promise to transform the current understanding of normal, abnormal, and malignant hematopoiesis. In this perspective, we discuss how the zebrafish model has proven beneficial for studying physiological and pathological hematopoiesis and how these novel technologies are transforming the field.

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Section: Identification Of Novel Regulatory Mechanisms Of Normal and mentioning

confidence: 99%

Bloody Zebrafish: Novel Methods in Normal and Malignant Hematopoiesis

Pater

Trompouki

2018

Front. Cell Dev. Biol.

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“…9,10 To date, only one arterially restricted enhancer located approximately 15-kb upstream of the notch1b first exon in zebrafish has been identified. 11 No enhancer was founded in the largest validated human and mouse enhancer database, the VISTA Enhancer Browser, and in the zebrafish enhancer database CONDOR (Conserved Non-coding Orthologous Regions). Therefore, it is necessary to identify additional cardiac development-related enhancers of this gene.…”

Section: Introductionmentioning

confidence: 99%

Identification of a 42‐bp heart‐specific enhancer of the notch1b gene in zebrafish embryos

Wang

Yang

et al. 2019

Developmental Dynamics

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Background NOTCH1 plays a key role in the differentiation of ventricles, and mutations are strongly associated with both sporadic and familial bicuspid aortic valves. However, few heart‐specific enhancers have been identified to date. Results In this study, we investigated evolutionary conserved regions (ECRs) that might act as potential enhancers within the region approximately 150‐kb upstream and downstream of the NOTCH1 gene. Functional validation revealed that one 127‐bp ECR located ~85‐kb downstream of the NOTCH1 gene drives green fluorescent protein expression in the zebrafish embryo heart. Transcription factor (TF) prediction and core TF distribution analyses were performed to identify the core region. Dissection of ECR3 was performed to identify the 42‐bp sequence, which is sufficient for heart‐specific expression. In situ hybridization experiments showed that notch1b is expressed in the heart. Overexpression experiments in cells indicated that NKX2‐5 is critical for enhancer activity. Mutation of the NKX‐5 binding site significantly decreased reporter gene expression. Next, compared with the commonly used myocardium‐labeled zebrafish transgenic strain Tg(cmlc2: mCherry), this 42‐bp enhancer‐labeled stable line mediated a similar expression pattern but with a smaller core region. Conclusion This study identified a 42‐bp heart‐specific enhancer near the NOTCH1 gene and further verified its functional targeting by NKX2‐5.

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“…Our data suggest that methylglyoxal may target-specific component(s) of the Notch pathway to regulate NPC homeostasis. Therefore, we asked whether one target could be the Notch1 receptor itself since it initiates the signalling cascade and is under extensive regulation for precise cell fate decision [27][28][29][30][31][32] . To test whether methylglyoxal regulates Notch1 expression in NPCs, we electroporated control or Glo1 shRNAs and a nuclear EGFP plasmid into the E13.5 cortex and examined Notch1 protein expression by immunostaining EGFP+ cells 2 days later.…”

Section: Resultsmentioning

confidence: 99%

Methylglyoxal couples metabolic and translational control of Notch signalling in mammalian neural stem cells

et al. 2020

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Gene regulation and metabolism are two fundamental processes that coordinate the selfrenewal and differentiation of neural precursor cells (NPCs) in the developing mammalian brain. However, little is known about how metabolic signals instruct gene expression to control NPC homeostasis. Here, we show that methylglyoxal, a glycolytic intermediate metabolite, modulates Notch signalling to regulate NPC fate decision. We find that increased methylglyoxal suppresses the translation of Notch1 receptor mRNA in mouse and human NPCs, which is mediated by binding of the glycolytic enzyme GAPDH to an AU-rich region within Notch1 3ʹUTR. Interestingly, methylglyoxal inhibits the enzymatic activity of GAPDH and engages it as an RNA-binding protein to suppress Notch1 translation. Reducing GAPDH levels or restoring Notch signalling rescues methylglyoxal-induced NPC depletion and premature differentiation in the developing mouse cortex. Taken together, our data indicates that methylglyoxal couples the metabolic and translational control of Notch signalling to control NPC homeostasis.

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SoxF factors induce Notch1 expression via direct transcriptional regulation during early arterial development

Cited by 53 publications

References 70 publications

Bloody Zebrafish: Novel Methods in Normal and Malignant Hematopoiesis

Bloody Zebrafish: Novel Methods in Normal and Malignant Hematopoiesis

Identification of a 42‐bp heart‐specific enhancer of the notch1b gene in zebrafish embryos

Methylglyoxal couples metabolic and translational control of Notch signalling in mammalian neural stem cells

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