Ask about this productRelated genes to: EVI1 antibody
- Gene:
- MECOM NIH gene
- Name:
- MDS1 and EVI1 complex locus
- Previous symbol:
- MDS1, EVI1
- Synonyms:
- MDS1-EVI1, PRDM3, KMT8E
- Chromosome:
- 3q26.2
- Locus Type:
- gene with protein product
- Date approved:
- 1990-07-10
- Date modifiied:
- 2019-04-23
Related products to: EVI1 antibody
Related articles to: EVI1 antibody
- MECOM is a transcription factor critical for the maintenance of hematopoietic stem cells (HSCs) and the pathogenesis of myeloid leukemia. Germline mutations clustered in the C-terminal zinc finger domain (ZFD) of MECOM are known to cause MECOM-associated syndromes, involving bone marrow failure and skeletal anomalies. However, the molecular consequences of these mutations and the precise downstream mechanisms of MECOM remain elusive. Here, we demonstrate that the C-terminal ZFD serves as the dominant DNA-binding module of MECOM, and that disease-associated mutations abrogate its DNA-binding capacity. Mechanistically, we reveal that MECOM functionally antagonizes GATA2 via C-terminal ZFD-mediated DNA binding and recruitment of the corepressor CtBP. This repression promotes myeloid leukemogenesis while suppressing mast cell differentiation. Furthermore, we generated a knockin mouse model harboring a C-terminal ZFD mutation, which successfully recapitulated the clinical phenotypes of MECOM-associated syndromes, including reduction of HSCs and B cells. Collectively, our findings define C-terminal ZFD mutations as loss-of-function mutations with impaired DNA binding, uncover the MECOM-GATA2 axis as a key regulatory pathway, and provide a valuable mouse model for understanding MECOM-associated syndromes. - Source: PubMed
Publication date: 2026/05/05
Iida KoheiNakanishi MayukoNakahara JakushinAsada ShuheiIsobe TomoyaYabushita TomohiroFukushima TsuyoshiTanaka YosukeOzawa ManabuYamada YasuhiroKitamura ToshioYamamoto KeitaGoyama Susumu - Alcohol consumption triggers neuroinflammation, potentially creating a feed-forward loop that increases drinking. Previous studies have shown that activation of the toll-like receptor 7 (TLR7) leads to escalated drinking. In this study, we aim to identify cell type-specific transcriptomic patterns underlying TLR7-induced neuroinflammation, potentially leading to escalated drinking. Therefore, male C57BL/6J mice were treated with the selective TLR7 agonist R848 every-other day for 20 days in total. After 10 treatment-free days, half of the cohort underwent two bottle-choice drinking; the other half was sacrificed and brains were collected for single-nucleus RNA-Sequencing (snRNA-Seq) in the medial prefrontal cortex (mPFC) and central amygdala (AMG). The AMG showed a greater number of differentially expressed genes (DEGs), primarily in inhibitory and excitatory neurons. Among glial cells, AMG astrocytes exhibited the greatest number of DEGs, which were involved in blood-brain barrier (BBB) regulation (e.g., Cldn5, Mecom, Nrg1), a finding supported by secondary validation using Xenium in situ spatial transcriptomics on AMG-containing sections. BBB-regulatory genes, including those in the Wnt signaling pathway (e.g., Notch3, Top2a, Aldoc), were altered across multiple cell types in both regions. Together with the alterations observed in neurons, these findings suggest that repeated TLR7 activation induces persistent BBB and neuronal dysregulation, potentially leading to TLR7-induced escalated drinking. - Source: PubMed
Publication date: 2026/04/30
Friske Marion MBarchiesi RiccardoSalem Nihal AAllard Ruth LDobre Anna CRhyan NicholasChen WenMayfield R Dayne - Congenital radioulnar synostosis (CRUS) is a forearm deformity caused by embryonic development disorder, characterized by limited forearm rotation, which can significantly impair patients' daily lives. The pathogenesis of CRUS has not been fully elucidated; with the advancement of whole-exome sequencing (WES) technology, a growing number of related gene mutations have been identified. - Source: PubMed
Publication date: 2026/02/26
Wang XiaoqingQu YuMa BingWang Hengbing - The gene MDS1 and EVI1 complex locus (MECOM) functions as a transcriptional regulator essential for development. Variants in MECOM have been recognized as pathogenic drivers, with well-established links to oncologic and hematopoietic disorders and increasing evidence for roles in cardiovascular diseases. Here, we examine the spectrum of MECOM variants and their connections to human diseases by integrating findings from genome-wide association studies (GWAS), expression quantitative trait loci (eQTL) analyses, and curated databases, together with single-case reports from whole-exome (WES) and whole-genome sequencing (WGS). Combining insights from both common and rare variants, we provide a comprehensive review of MECOM's genetic landscape and outline how specific alterations contribute to pathogenic mechanisms. We also highlight strategies targeting MECOM and the urgent need to investigate MECOM-associated single-nucleotide polymorphisms (SNPs) as both mechanistic drivers and potential therapeutic targets. - Source: PubMed
Publication date: 2026/04/03
Chen JiayiVenkatesh AnirudhChen KaifuZhang Lili - Regulated in development and DNA damage response-1 (REDD1/DDIT4) is induced in response to environmental stress to restrain the mechanistic target of rapamycin complex 1 (mTORC1) signaling as an adaptive strategy to restore cellular homeostasis. Interestingly, REDD1/DDIT4 expression is upregulated in several tumor types including colorectal cancer, suggesting it may have a role in tumourigenesis. Here, we report that activating transcription factor 4 (ATF4)-dependent REDD1/DDIT4 expression is required for survival of colon tumor cells undergoing endoplasmic reticulum (ER) stress through the modulation of TRAILR2/DR5 gene expression. Our findings further demonstrate that resistance to ER stress-induced apoptosis in multicellular tumor spheroids (MCTS) is associated with constitutive expression of REDD1/DDIT4 and diminished mTORC1 activity. CRISPR/Cas9-mediated deletion of REDD1/DDIT4 markedly increases TRAILR2/DR5 expression and enhances apoptosis in spheroids exposed to ER stress. Interestingly, RNA sequencing analysis reveals that the loss of the transcriptional regulator EVI-1/MECOM in cells deficient in REDD1/DDIT4 amplifies the ER stress-induced upregulation of TRAILR2/DR5, leading to enhanced apoptosis. In summary, our findings underscore the crucial role of REDD1/DDIT4 in regulating TRAILR2/DR5-induced caspase-8 activation and apoptosis under chronic ER stress, by inhibiting mTORC1 activity and promoting EVI-1/MECOM-mediated suppression of TRAILR2/DR5 gene expression. - Source: PubMed
Publication date: 2026/03/28
Mora-Molina RocíoEl Yousfi YounesHagenlocher CathrinFernández-Farrán Francisco JavierRehm MarkusPalacios CarmenChristophorou Maria ALópez-Rivas Abelardo