Ask about this productRelated genes to: AHCY protein
- Gene:
- AHCY NIH gene
- Name:
- adenosylhomocysteinase
- Previous symbol:
- -
- Synonyms:
- SAHH
- Chromosome:
- 20q11.22
- Locus Type:
- gene with protein product
- Date approved:
- 1986-01-01
- Date modifiied:
- 2018-05-03
Related products to: AHCY protein
Related articles to: AHCY protein
- Intermittent fasting (IF) ameliorates metabolic dysfunction-associated steatotic liver disease (MASLD), but the underlying mechanism remains unclear. Combined CUT&Run and transcriptomic analysis shows that hepatic Ahcy is controlled by the super‑enhancer (SE) and acts as a key mediator of IF's benefit. Liver‑specific Ahcy knockout worsens high‑fat diet (HFD)‑induced hepatic steatosis and blunts the protective effect of IF. Furthermore, inhibition of Brd4 or deletion of the core SE region reduces Ahcy expression and exacerbates lipid accumulation in vivo or in vitro. Hnf4a is identified as the transcription factor driving the Ahcy-SE. In vitro and in vivo experiments demonstrate that IF-activated Hnf4a directly binds to and activates the Ahcy-SE. Ahcy knockdown attenuates the lipid-deposition-reducing effect of Hnf4a overexpression in mice fed a HFD. In Ahcy mice, the liver SAM/SAH ratio is reduced, and Reduced Representation Bisulfite Sequencing (RRBS) and transcriptome sequencing reveal liver-specific methylation remodeling. One manifestation of this remodeling is hypermethylation of metabolic gene promoters, including the Acot12 promoter, where aberrant recruitment of Dnmt3b leads to silencing of the gene and impaired lipid hydrolysis. Therefore, these findings define an IF-Hnf4a-Ahcy pathway that activates SE-driven Ahcy to orchestrate protective epigenetic reprogramming in MASLD. - Source: PubMed
Publication date: 2026/07/27
Chen HuafengZhang ShilinDeng XiaojieXie WenqiangXu FenShen JieLiang Hua - Cardiogenic shock secondary to acute myocardial infarction (AMI-CS) prohibitively impacts survival. This prospective study aimed to discover and internally verify candidate serum protein biomarkers and evaluate their potential prognostic value for 30-day mortality in AMI-CS patients. - Source: PubMed
Publication date: 2026/07/20
Wang XiXiao Qian-FengHuang Fang-YangWang SiXu YingPu Xiao-BoYang YanChen MaoWei Xin - Methionine cycle plays critical roles in cell fate determination by shaping epigenetic landscape, yet its function in human erythropoiesis remains undefined. Here, we show that disruption of methionine metabolism by compromising key enzyme adenosylhomocysteinase (AHCY) reshapes H3K4me3 landscape, causing erythroid cell fate reprogramming. AHCY deficiency severely impaired erythroid differentiation and expansion, leading to the generation of non-erythroid lineage hematopoietic cells, including stem/progenitor cells and immune cells, as evidenced by single-cell RNA sequencing, Pseudo temporal analysis delineated a precise dedifferentiation trajectory, revealing erythroblasts transitioning back to MEPs and HSCs. Moreover, human hematopoietic system could be reconstituted in the immunodeficient NCG-X mice by transplanting AHCY deficient erythroblasts. Mechanistically, AHCY deficiency reduced global H3K4me3 levels and altered its genomic distribution, resulting in the upregulated expression of non-erythroid transcription factors and downregulated expression of erythrocyte lineage-specific transcription factors. Integrated single-cell analyses identified transitional states with diminished AHCY in the erythroblasts of acute myeloid leukemia (AML) patient. Further flow cytometry confirmed the reduced H3K4me3 level in patient derived erythroid cells. Erythroblasts isolated from AML patients with reduced H3K4me3 exhibited dedifferentiation potential into progenitor-like states. Our findings reveal a metabolic-epigenetic axis governing cell fate reprogramming in human erythropoiesis and provide insights into leukemia associated anemia. - Source: PubMed
Publication date: 2026/07/14
Sun LeiZhang HengchaoLi MengjiaLin QuandeWu XiuyunCheng YingWang ShihuiHou YanWang YaomeiSheng YueLiu JingAn XiuliWang TingChen Lixiang - Methylation of DNA, histones, and RNA is central to the regulation of circadian rhythms, yet the biochemical origin of the methyl groups driving these modifications has received comparatively little attention in circadian biology. This review explores the bidirectional crosstalk between the methyl cycle and the mammalian circadian clock. We describe how S-adenosylmethionine-dependent epigenetic and epitranscriptomic modifications constitute essential layers of circadian gene regulation, and how the clock orchestrates the rhythmic expression of one-carbon metabolism enzymes and oscillations in S-adenosylmethionine availability. The direct interaction between the S-adenosylhomocysteine hydrolase AHCY and the core clock component BMAL1 at circadian gene promoters emerges as a molecular nexus linking methyl group supply to clock-driven transcription. We further discuss how the methyl cycle occupies a privileged position within the circadian entrainment hierarchy, acting as both a target of nutritional zeitgebers in peripheral tissues and a potential source of metabolic feedback to the central pacemaker, and how dietary perturbation of the methyl cycle disrupts circadian rhythms. Finally, we discuss how this crosstalk is implicated in metabolic liver disease, cancer, neurological disorders, and aging. Together, these findings position the circadian clock as a sensitive readout of nutritional methyl metabolic status, with broad implications for chronobiology and nutrigenomics. - Source: PubMed
Publication date: 2026/07/01
Fustin Jean-Michel - This study investigates how hypoxia remodels the extracellular vesicle (EV) proteome to promote metastasis in breast cancer (BC) cells. EVs from hypoxic MCF-7 and MDA-MB-231 cells were characterized and shown to enhance epithelial-mesenchymal transition (EMT), migration, invasion, and clonogenicity in recipient cells. Quantitative proteomics identified over 1250 EV proteins, with 78 commonly regulated by hypoxia across both cell lines. Pathway analysis revealed hypoxia-induced EV enrichment of ribosomal, chromatin remodeling, mitochondrial, and one-carbon metabolism proteins, alongside depletion of immune-modulatory factors. Interestingly, key one-carbon metabolism enzymes (SMS, CAD, and AHCYL1) were consistently upregulated in hypoxic EVs shed by both the cell lines. Notably, AHCYL1, a regulator of the methylation cycle enzyme AHCY, is significantly upregulated under hypoxic conditions. Our findings demonstrate that hypoxic EVs promote an increase in histone H3K9 trimethylation levels in recipient cells. This epigenetic shift downregulated epithelial and metastasis-suppressor genes (CDH1, EpCAM, and DKK1) while sustaining expression of EMT transcription factors (ZEB1 and SNAIL), thereby stabilizing EMT and enhancing invasiveness. Collectively, we describe a hypoxia-driven EV proteome that links metabolic reprogramming to epigenetic enforcement of metastatic traits in BC. - Source: PubMed
Publication date: 2026/06/24
Bhavsar VaidehiSahu AshishKarandikar AkhilTaware Ravindra