Immunity, Год журнала: 2024, Номер unknown
Опубликована: Дек. 1, 2024
Язык: Английский
Trends in Biochemical Sciences, Год журнала: 2025, Номер unknown
Опубликована: Янв. 1, 2025
Язык: Английский
Процитировано
1
Nature Immunology, Год журнала: 2024, Номер 25(9), С. 1580 - 1592
Опубликована: Авг. 21, 2024
Abstract Transcriptional condensates play a crucial role in gene expression and regulation, yet their assembly mechanisms remain poorly understood. Here, we report multi-layered mechanism for condensate by autoimmune regulator (Aire), an essential transcriptional that orchestrates reprogramming central T cell tolerance. Aire assemble on enhancers, stimulating local activities connecting disparate inter-chromosomal loci. This functional formation hinges upon the coordination between three domains: polymerization domain caspase activation recruitment (CARD), histone-binding (first plant homeodomain (PHD1)), C-terminal tail (CTT). Specifically, CTT binds coactivators CBP/p300, recruiting to CBP/p300-rich enhancers promoting CARD-mediated assembly. Conversely, PHD1 ubiquitous histone mark H3K4me0, keeping dispersed throughout genome until nucleates enhancers. Our findings showed balance PHD1-mediated suppression CTT-mediated stimulation of is form transcriptionally active at target sites, providing new insights into controlled regulators.
Язык: Английский
Процитировано
5
Advances in experimental medicine and biology, Год журнала: 2025, Номер unknown, С. 199 - 221
Опубликована: Янв. 1, 2025
Язык: Английский
Процитировано
0
Nucleic Acids Research, Год журнала: 2025, Номер 53(5)
Опубликована: Фев. 27, 2025
We discovered that the Z-form DNA-RNA hybrid stabilized by methylated CpG repeats impacts on initiation and elongation of Okazaki fragments, contributing to blocking DNA replication at first time. further present structure using NMR spectroscopy dynamic computation, revealing molecular mechanism inhibition, indicating a distinctive zig-zag strand pattern with smaller helical diameter (15 Å) very narrow minor groove (8.3 plays key role in repression toward replication.
Язык: Английский
Процитировано
0
New England Journal of Medicine, Год журнала: 2024, Номер 390(20), С. 1918 - 1921
Опубликована: Май 29, 2024
Язык: Английский
Процитировано
2
Nature Reviews Genetics, Год журнала: 2024, Номер 25(6), С. 375 - 375
Опубликована: Март 27, 2024
Язык: Английский
Процитировано
1
Current Opinion in Allergy and Clinical Immunology, Год журнала: 2024, Номер 24(6), С. 448 - 456
Опубликована: Окт. 23, 2024
The purpose of the review is to describe most recent advancement in understanding pivotal role autoimmune regulator ( AIRE ) gene expression central and peripheral tolerance, implications its impairment genetic pathogenesis polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) manifestations with insight into possible treatment options.
Язык: Английский
Процитировано
1
Pharmacological Reviews, Год журнала: 2024, Номер 77(2), С. 100032 - 100032
Опубликована: Дек. 24, 2024
Vitamin D was discovered as the cure for nutritional rickets, a disease of bone growth arising from inadequate intestinal calcium absorption, and much 20th century, it studied its critical role in homeostasis. However, we now recognize that vitamin receptor metabolic enzymes are expressed numerous tissues unrelated to Notably, signaling can induce cellular differentiation cell cycle arrest. Moreover, enzyme CYP27B1, which produces hormonal form D, 1,25-dihydroxyvitamin (1,25D), throughout immune system. In addition, CYP27B1 expression cells is regulated by physiological inputs independent those controlling homeostatic tissues. These observations have driven development 1,25D-like secosteroidal analogs nonsecosteroidal separate effects on function calcemic activities. some these had considerable success clinic treatment inflammatory immune-related disorders. this review, described detail mechanisms signals 1,25D synthesis catabolism, with focus We also surveyed regulation system their implications human Finally, potential anticancer therapeutics, particular, use adjuncts cancer immunotherapy. SIGNIFICANCE STATEMENT: active both innate adaptive arms Numerous analogs, developed primarily minimize dose-limiting hypercalcemia been used widely preclinical clinical studies regulation. This review presents description action signaling, an overview analog development, in-depth discussion immunoregulatory roles analogs.
Язык: Английский
Процитировано
1
Elsevier eBooks, Год журнала: 2024, Номер unknown
Опубликована: Янв. 1, 2024
Язык: Английский
Процитировано
0
bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown
Опубликована: Дек. 10, 2024
Abstract The Autoimmune Regulator, AIRE, acts as a transcriptional regulator in the thymus, facilitating ectopic expression of thousands genes important for process negative T-cell selection and immunological tolerance to self. Pathogenic variants gene encoding AIRE are causing polyendocrine syndrome type 1 (APS-1), defined by multiorgan autoimmunity chronic mucocutaneous candidiasis. More recently, Genome Wide Association Studies (GWAS) have also implicated several common organ-specific autoimmune diseases including primary adrenal insufficiency, diabetes pernicious anemia. We developed highly sensitive cell-system approach based on HEK293FT cells transfected with that allowed us characterise functionally evaluate potential genetic gene. confirm our cell system recapitulates vast majority known induced well-characterised tissue restricted antigens (TRAs), but increases total number identified an order magnitude compared previously published strategies. differentiates between categories level, nonsense variant p.R257* (near complete loss function), p.C311Y associated dominantly inherited APS-1 (severely impaired polygenic risk p.R471C (slightly increased function) linked autoimmunity. activity wildtype indicates different molecular mechanisms monogenic related
Язык: Английский
Процитировано
0