SAHH x PRC2

Last update 08 May 2025

Basic Info

Related Targets

SAHHPRC2

Drugs associated with SAHH x PRC2

3-deazaneplanocin A

Target

PRC2 x SAHH

Mechanism

Polycomb repressive complex 2 inhibitors [+1]

Active Org.

Kawasaki Medical School [+1]

Originator Org.

National Cancer Institute

Active Indication

Melanoma [+1]

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with SAHH x PRC2

100 Translational Medicine associated with SAHH x PRC2

0 Patents (Medical) associated with SAHH x PRC2

Literatures (Medical) associated with SAHH x PRC2

01 Jun 2025·Journal of Oral Biosciences

Impact of DLX3/SAHH axis on osteogenic differentiation of BMSCs in alveolar bone

Article

Author: Chen, Xinyi ; Chen, Kang ; Sun, Haipeng ; Jiang, Yuxi ; Chai, Jinyou ; Sun, Shichen

OBJECTIVESBone marrow mesenchymal stem cells (BMSCs) promote alveolar bone formation and repair. Distal-less homeobox 3 (DLX3) plays a key regulatory role in BMSC osteogenesis. However, the precise pathway by which it mediates osteogenesis in BMSCs remains unclear. In this study, we investigated the potential epigenetic mechanisms underlying DLX3-mediated BMSCs osteogenesis.METHODSBMSCs were isolated from the alveolar bone. DLX3 overexpression and knockdown cell lines were established using lentivirus-mediated gene transfer. Osteogenic differentiation was evaluated using alkaline phosphatase expression, alizarin red staining, real-time quantitative polymerase chain reaction, western blotting, chromatin immunoprecipitation, RNA immunoprecipitation, and S-adenosyl-homocysteine hydrolase (SAHH) activity measurements.RESULTSDLX3 enhanced the osteogenic differentiation of BMSCs, positively regulated SAHH, and enhancer of zeste homolog 2 (EZH2) activity. In addition, the long non-coding RNA H19 (H19) bound to SAHH in BMSCs. DLX3 regulated the expression of H19, and rescue experiments showed that H19 knockdown increased SAHH activity, thereby promoting osteogenic differentiation in the DLX3-overexpression group.CONCLUSIONSThe DLX3/SAHH axis may regulate the activity of EZH2 involved in the osteogenic differentiation of BMSCs.

13 Mar 2024·Biology of Reproduction

Adenosylhomocysteinase plays multiple roles in maintaining the identity and pluripotency of mouse embryonic stem cells

Article

Author: Wu, Guangming ; Zhang, Hui ; Guo, Zhencheng ; Liu, Zhonghua ; Tan, Fancheng ; Liang, Yiping ; Lan, Shubing ; Hou, Yanlin ; Jiang, Qi

AbstractAdenosylhomocysteinase (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.

01 Sep 2021·Redox BiologyQ1 · BIOLOGY

Epigenetic regulation of TXNIP-mediated oxidative stress and NLRP3 inflammasome activation contributes to SAHH inhibition-aggravated diabetic nephropathy

Q1 · BIOLOGY

ArticleOA

Author: Guo, Honghui ; Ling, Wenhua ; Jin, Tianru ; Dai, Xin ; Liu, Si ; Xia, Min ; Zheng, Zhihua ; Liu, Chaoqun ; Huang, Haiyan ; Xiao, Yunjun ; Liu, Jianjun ; Liao, Ruyi

S-adenosylhomocysteine (SAH) is hydrolyzed by SAH hydrolase (SAHH) to homocysteine and adenosine. Increased plasma SAH levels were associated with disturbed renal function in patients with diabetes. However, the role and mechanism of SAHH in diabetic nephropathy is still unknown. In the present study, we found that inhibition of SAHH by using its inhibitor adenosine dialdehyde (ADA) accumulates intracellular or plasma SAH levels and increases high glucose-induced podocyte injury and aggravates STZ-induced diabetic nephropathy, which is associated with Nod-like receptor protein 3 (NLRP3) inflammasome activation. Inhibition or knockout of NLRP3 attenuates SAHH inhibition-aggravated podocyte injury and diabetic nephropathy. Additionally, SAHH inhibition increases thioredoxin-interacting protein (TXNIP)-mediated oxidative stress and NLRP3 inflammasome activation, but these effects were not observed in TXNIP knockout mice. Mechanistically, SAHH inhibition increased TXNIP by inhibiting histone methyltransferase enhancer of zeste homolog 2 (EZH2) and reduced trimethylation of histone H3 lysine 27 and its enrichment at promoter of early growth response 1 (EGR1). Moreover, EGR1 is activated and enriched at promoters of TXNIP by SAHH inhibition and is essential for SAHH inhibition-induced TXNIP expression. Inhibition of EGR1 protected against SAHH inhibition-induced NLRP3 inflammasome activation and oxidative stress and diabetic nephropathy. Finally, the harmful effects of SAHH inhibition on inflammation and oxidative stress and diabetic nephropathy were also observed in heterozygote SAHH knockout mice. These findings suggest that EZH2/EGR1/TXNIP/NLRP3 signaling cascade contributes to SAHH inhibition-aggravated diabetic nephropathy. Our study firstly provides a novel insight into the role and mechanism of SAHH inhibition in diabetic nephropathy.

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