Impaired neuronal differentiation is a feature of neuroblastoma tumorigenesis, and the differentiation grade of neuroblastoma tumors is associated with patient prognosis. Detailed understanding of the molecular mechanisms underlying neuroblastoma differentiation will facilitate the development of effective treatment strategies. Recent studies have shown that myelin transcription factor 1 (MYT1) promotes vertebrate neurogenesis by regulating gene expression. We performed quantitative analysis of neuroblastoma samples, which revealed that MYT1 was differentially expressed among neuroblastoma patients with different pathological diagnoses. Analysis of clinical data showed that MYT1 overexpression was associated with a significantly shorter 3-year overall survival rate and poor differentiation in neuroblastoma specimens. MYT1 knockdown inhibited proliferation and promoted the expression of multiple differentiation-associated proteins. Integrated omics data indicated that many genes involved in neuro-differentiation were regulated by MYT1. Interestingly, many of these genes are targets of the REST complex; therefore, we further identified the physical interaction of MYT1 with LSD1/CoREST. Depletion of LSD1 or inhibition of LSD1 by ORY-1001 decreased MYT1 expression, providing an alternative approach to target MYT1. Taken together, our results indicate that MYT1 significantly attenuates cell differentiation by interacting with the LSD1/CoREST complex. MYT1 is, therefore, a promising therapeutic target for enhancing the neurite-inducing effect of retinoic acid and for inhibiting the growth of neuroblastoma.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1038/s41388-020-1268-6 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Myelin Transcription Factor 1 (MyT1) overexpression mitigates social isolation-induced behavioral deficits: Insights into cortical synaptotagmin 1 regulation and antidepressant-like effects.
Pharmacol Biochem Behav
January 2025
Division of Biochemistry, University of Fribourg, Fribourg, Switzerland.
Social isolation (SI) stress is increasingly recognized as a concern, associated with detrimental effects on mood and emotional well-being. Myelin Transcription Factor 1 (MyT1) is known for its pivotal role in nervous system development and mood regulation. This study delves into the potential of MyT1 to mitigate SI-induced behavioral abnormalities in mice.
View Article and Find Full Text PDFNeuronal splicing of the unmethylated histone H3K4 reader, PHF21A, prevents excessive synaptogenesis.
J Biol Chem
November 2024
Department of Human Genetics, University of Michigan, Ann Arbor, Michigan, USA; Department of Pediatrics, University of Michigan Medical School, Ann Arbor, Michigan, USA; Michigan Neuroscience Institute, University of Michigan, Ann Arbor, Michigan, USA. Electronic address:
Article Synopsis
- PHF21A is a histone-binding protein that works with LSD1 and both proteins are important for neuron-specific splicing, impacting their functions in the brain.
- The study shows that during brain development, PHF21A expression happens before LSD1 expression, leading to reduced activity of their complex and altered methylation processes.
- PHF21A's unique microexon plays a crucial role in preventing excessive synapse formation by moderating LSD1's function, indicating its importance in proper neuronal development.
Cancer cell proliferation requires precise control of E2F1 activity; excess activity promotes apoptosis. Here, we developed cell-permeable and bioavailable macrocycles that selectively kill small cell lung cancer (SCLC) cells with inherent high E2F1 activity by blocking RxL-mediated interactions of cyclin A and cyclin B with select substrates. Genome-wide CRISPR/Cas9 knockout and random mutagenesis screens found that cyclin A/B RxL macrocyclic inhibitors (cyclin A/Bi) induced apoptosis paradoxically by cyclin B- and Cdk2-dependent spindle assembly checkpoint activation (SAC).
View Article and Find Full Text PDFMetabolic Stress Levels Influence the Ability of Myelin Transcription Factors to Regulate β-Cell Identity and Survival.
Diabetes
October 2024
Program in Developmental Biology, Department of Cell and Developmental Biology, Vanderbilt University School of Medicine, Nashville, TN.
Article Synopsis
- The study investigates how type 2 diabetes (T2D) is related to the failure of endocrine islet β-cells, focusing on the role of myelin transcription factors (Myt TFs) in this process.
- By using mouse models, researchers found that without Myt TFs, β-cells could dedifferentiate and reactivate progenitor markers, indicating a loss of identity and function.
- Results showed that environmental factors like blood sugar levels also impact β-cell health, suggesting that T2D is influenced by both genetic defects and metabolic stress.
Fine mapping of candidate effector genes for heart rate.
Hum Genet
October 2024
William Harvey Research Institute, Barts and the London Faculty of Medicine and Dentistry, Queen Mary University of London, London, EC1M 6BQ, UK.
An elevated resting heart rate (RHR) is associated with increased cardiovascular mortality. Genome-wide association studies (GWAS) have identified > 350 loci. Uniquely, in this study we applied genetic fine-mapping leveraging tissue specific chromatin segmentation and colocalization analyses to identify causal variants and candidate effector genes for RHR.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!