Adenosylhomocysteinase (AHCY), a key enzyme in the methionine cycle, is essential for the development of embryos and the maintenance of mouse embryonic stem cells (mESCs). However, the precise underlying mechanism of Ahcy in regulating pluripotency remains unclear. As the only enzyme that can hydrolyze S-adenosylhomocysteine in mammals, AHCY plays a critical role in the metabolic homeostasis, epigenetic remodeling, and transcriptional regulation. Here, we identified Ahcy as a direct target of OCT4 and unveiled that AHCY regulates the self-renewal and differentiation potency of mESCs through multiple mechanisms. Our study demonstrated that AHCY is required for the metabolic homeostasis of mESCs. We revealed the dual role of Ahcy in both transcriptional activation and inhibition, which is accomplished via the maintenance of H3K4me3 and H3K27me3, respectively. We found that Ahcy is required for H3K4me3-dependent transcriptional activation in mESCs. We also demonstrated that AHCY interacts with polycomb repressive complex 2 (PRC2), thereby maintaining the pluripotency of mESCs by sustaining the H3K27me3-regulated transcriptional repression of related genes. These results reveal a previously unrecognized OCT4-AHCY-PRC2 axis in the regulation of mESCs' pluripotency and provide insights into the interplay between transcriptional factors, cellular metabolism, chromatin dynamics and pluripotency regulation.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1093/biolre/ioad165 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Dysmorphic Findings in SAHH Deficiency with a Novel Variant in the Gene.
Mol Syndromol
December 2024
Department of Medical Genetics, University of Health Sciences, Van Training and Research Hospital, Van, Turkey.
Introduction: S-adenosylhomocysteine hydrolase (SAHH) is one of the enzymes involved in converting methionine to homocysteine with transmethylation processes. Methyltransfer reactions are impaired in SAHH deficiency. SAHH deficiency is multisystemic and antenatal onset disorder.
View Article and Find Full Text PDFMAT2a and AHCY inhibition disrupts antioxidant metabolism and reduces glioblastoma cell survival.
bioRxiv
November 2024
Georgetown University, Lombardi Comprehensive Cancer Center, 3970 Reservoir Rd NW Washington D.C. 20007, United States of America.
Glioblastoma (GBM) is a highly aggressive primary malignant adult brain tumor that inevitably recurs with a fatal prognosis. This is due in part to metabolic reprogramming that allows tumors to evade treatment. We therefore must uncover the pathways mediating these adaptations to develop novel and effective treatments.
View Article and Find Full Text PDFGenome-wide DNA methylation regulated by AHCY through SAM / SAH axis promotes psoriasis pathogenesis.
J Dermatol Sci
December 2024
Institute of Dermatology and Hospital for Skin Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College, Nanjing, China. Electronic address:
Article Synopsis
- Psoriasis is a widespread chronic skin condition, and the role of S-adenosine homocysteine hydrolase (AHCY) in its development and its effects on DNA methylation had not been thoroughly examined.
- This study explored how AHCY expression in psoriatic lesions relates to disease severity and its effects on keratinocyte behavior and DNA methylation through knockdown experiments.
- The results show that AHCY is elevated in psoriasis, contributes to disease severity, and alters DNA methylation patterns, suggesting that targeting AHCY could be a potential therapeutic approach for treating psoriasis.
Asymptomatic pediatric presentation of S-adenosylhomocysteine hydrolase deficiency.
JIMD Rep
November 2024
Article Synopsis
- S-adenosylhomocysteine hydrolase deficiency is an autosomal recessive metabolic disorder disrupting the methionine cycle, which can range from severe symptoms to asymptomatic cases.
- Two clinically asymptomatic siblings from Pakistan were diagnosed with mild chronic liver failure and other mild symptoms, with one sibling showing improvements after dietary changes.
- The research highlights a specific genetic variant common in South Asia and suggests this milder form of the disease may be underdiagnosed, emphasizing the need for better therapeutic management to prevent future health complications.
Transcriptional changes impact hepatic proteome in autophagy-impaired liver.
FEBS Open Bio
November 2024
Department of Pathology and Laboratory Medicine, Tulane University School of Medicine, New Orleans, LA, USA.
Article Synopsis
- The study focuses on how autophagy impacts the hepatic proteome, especially regarding the degradation and regulation of liver proteins.
- Researchers found that when autophagy is impaired, certain proteins like Cps1, Ahcy, and Ca3 decrease, while Gstm1 increases due to changes in mRNA levels rather than just degradation.
- The results highlight that autophagy affects liver proteins not only through degradation but also by influencing gene expression via the Nrf2 transcription factor.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!