Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027819 (neuroblastoma)
 27,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Regulation of spatiotemporal gene expression in higher eukaryotic cells is critical for the precise and orderly development of undifferentiated progenitors into committed cell types of the adult. It is well known that dynamic epigenomic regulation (including chromatin remodeling and histone modifications by transcriptional coregulator complexes) is involved in transcriptional regulation. Precisely how these coregulator complexes exert their cell type and developing stage-specific activity is largely unknown. In this study we aimed to isolate the histone demethylase lysine-specific demethylase 1 (LSD1) complex from neural cells by biochemical purification. In so doing, we identified myelin transcription factor 1 (MyT1) as a novel LSD1 complex component. MyT1 is a neural cell-specific zinc finger factor, and it forms a stable multiprotein complex with LSD1 through direct interaction. Target gene analysis using microarray and ChIP assays revealed that the Pten gene was directly regulated by the LSD1-MyT1 complex. Knockdown of either LSD1 or MyT1 derepressed the expression of endogenous target genes and inhibited cell proliferation of a neuroblastoma cell line, Neuro2a. We propose that formation of tissue-specific combinations of coregulator complexes is a critical mechanism for tissue-specific transcriptional regulation.
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PMID:Identification of myelin transcription factor 1 (MyT1) as a subunit of the neural cell type-specific lysine-specific demethylase 1 (LSD1) complex. 2482 97

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.
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PMID:MYT1 attenuates neuroblastoma cell differentiation by interacting with the LSD1/CoREST complex. 3225 64