Neuropharmacology, Год журнала: 2023, Номер 239, С. 109682 - 109682
Опубликована: Авг. 3, 2023
Язык: Английский
Cellular and Molecular Life Sciences, Год журнала: 2020, Номер 78(6), С. 2517 - 2563
Опубликована: Дек. 2, 2020
Abstract Neurodevelopmental disorders (NDDs), including intellectual disability (ID) and autism spectrum (ASD), are a large group of in which early insults during brain development result wide heterogeneous clinical diagnoses. Mutations genes coding for chromatin remodelers overrepresented NDD cohorts, pointing towards epigenetics as convergent pathogenic pathway between these disorders. In this review we detail the role NDD-associated developmental continuum progenitor expansion, differentiation, cell-type specification, migration maturation. We discuss how defects remodelling time points compound over impaired circuit establishment. particular, focus on their three largest cell populations: glutamatergic neurons, GABAergic glia cells. An in-depth understanding spatiotemporal neurodevelopment can contribute to identification molecular targets treatment strategies.
Язык: Английский
Процитировано
82
Journal of Molecular Cell Biology, Год журнала: 2021, Номер 13(7), С. 480 - 499
Опубликована: Июль 1, 2021
Obesity has reached epidemic proportions globally. Although modern adoption of a sedentary lifestyle coupled with energy-dense nutrition is considered to be the main cause obesity epidemic, genetic preposition contributes significantly imbalanced energy metabolism in obesity. However, variants loci identified from large-scale studies do not appear fully explain rapid increase last four five decades. Recent advancements next-generation sequencing technologies and tissue-specific effects epigenetic factors metabolic organs have advanced our understanding regulation The epigenome, including DNA methylation, histone modifications, RNA-mediated processes, characterized as mitotically or meiotically heritable changes gene function without alteration sequence. Importantly, modifications are reversible. Therefore, comprehensively landscape could unravel novel molecular targets for treatment. In this review, we summarize current knowledge on roles such methylation acetylation, processes regulating metabolism. We also discuss therapeutic agents
Язык: Английский
Процитировано
61
Nature Genetics, Год журнала: 2022, Номер 54(5), С. 625 - 636
Опубликована: Май 1, 2022
Язык: Английский
Процитировано
50
Molecular Cell, Год журнала: 2023, Номер 83(9), С. 1412 - 1428.e7
Опубликована: Апрель 24, 2023
Язык: Английский
Процитировано
24
Molecular Neurobiology, Год журнала: 2023, Номер 60(11), С. 6476 - 6529
Опубликована: Июль 17, 2023
Язык: Английский
Процитировано
24
Epigenetics & Chromatin, Год журнала: 2025, Номер 18(1)
Опубликована: Янв. 17, 2025
DNA methylation, catalyzed by methyltransferases (DNMT), plays pivotal role in regulating embryonic development, gene expression, adaption to environmental stress, and maintaining genome integrity. DNMT family consists of DNMT1, DNMT3A, DNMT3B, the enzymatically inactive DNMT3L. DNMT3A DNMT3B establish novel methylation patterns maintained DNMT1 during replication. Genetic variants cause rare diseases such as Tatton-Brown-Rahman ICF syndromes. Additionally, somatic mutations common conditions osteoarthritis, osteoporosis, clonal hematopoiesis indeterminate potential (CHIP), hematologic malignancies, cancer. While DNMTs have been extensively studied vitro, early development disease, their detailed physiologic roles remain less understood vivo investigations are hindered or perinatal lethality knockout mice. To circumvent this problem, tissue-specific Dnmt3a Dnmt3b knockouts were engineered. This review explores diverse molecular across various organs cell types characterizes phenotype We provide a comprehensive collection over forty models generated cre recombinase. highlight distinct functions germ cells, uterus, hematopoietic differentiation, musculoskeletal visceral organs, nervous system. Our findings indicate that primarily regulates while is crucial for cartilage homeostasis ossification. emphasize context-dependent demonstrate they also complement maintenance methyltransferase activity. Overall, expression tissues insights into therapeutic applications treating neurologic diseases, cancer, osteoporosis.
Язык: Английский
Процитировано
2
Communications Biology, Год журнала: 2025, Номер 8(1)
Опубликована: Фев. 4, 2025
Enzalutamide is a potent second-generation antiandrogen commonly used to treat hormone-sensitive and castration-resistant prostate cancer (CRPC) patients. While initially effective, the disease almost always develops resistance. Given that many enzalutamide-resistant tumors lack specific somatic mutations, there strong evidence epigenetic factors can cause enzalutamide To explore how resistance arises, we systematically test all modifiers in several models of with custom CRISPR library. From this, identify validate SMARCC2, core component SWI/SNF complex, selectivity essential models. We show chromatin occupancy SMARCC2 BRG1 expanded at regions overlap CRPC-associated transcription are accessible CRPC clinical samples. Overall, our study reveals regulatory role for supports feasibility targeting complex late-stage PCa. An epigenome-focused screen identified unique dependency against complexes potentially mediated by an expansion their binding regions.
Язык: Английский
Процитировано
1
Current Opinion in Neurobiology, Год журнала: 2025, Номер 92, С. 102990 - 102990
Опубликована: Март 3, 2025
Язык: Английский
Процитировано
1
Science, Год журнала: 2021, Номер 372(6549)
Опубликована: Июнь 25, 2021
MeCP2 binds hydroxymethylated CA repeats Despites of decades research on the Rett syndrome protein MeCP2, its function remains unclear. Ibrahim et al. show that is a cytosine-adenosine (CA) repeat-binding modulates chromatin architecture at distance from transcription start site (see Perspective by Zhou and Zoghbi). accumulates spreads around modified competes for nucleosome occupancy. Loss results in widespread increase density inside lamina-associated domains transcriptional dysregulation genes enriched repeats. These shed light underlying molecular mechanism syndrome, severe disease associated with mutations MeCP2. Science , abd5581, this issue p. eabd5581 ; see also abj5027, 1390
Язык: Английский
Процитировано
50
Cells, Год журнала: 2021, Номер 10(10), С. 2679 - 2679
Опубликована: Окт. 6, 2021
Mounting evidence implicates microRNAs (miRNAs) in the pathology of schizophrenia. These small noncoding RNAs bind to mRNAs containing complementary sequences and promote their degradation and/or inhibit protein synthesis. A single miRNA may have hundreds targets, targets are overrepresented among schizophrenia-risk genes. Although schizophrenia is a neurodevelopmental disorder, symptoms usually do not appear until adolescence, most patients receive diagnosis late adolescence or early adulthood. However, few studies examined miRNAs during this critical period. First, we examine that pathway dynamic throughout adulthood regulate processes neurodevelopment aberrant with Next, implicating conversion psychosis, including schizophrenia-associated nucleotide polymorphism MIR137HG strongest known predictors age onset Finally, how hemizygosity for DGCR8, which encodes an obligate component complex synthesizes precursors, contribute psychosis 22q11.2 microdeletions animal models disorder can help us understand many roles
Язык: Английский
Процитировано
42